Skip to main content
Download PDF

Clinical significance of circulating long non-coding RNA SNHG1 in type 2 diabetes mellitus and its association with cell proliferation of pancreatic β-cell

BMC Endocrine Disorders volume 24, Article number: 225 (2024) Cite this article

Abstract

Background

To explore the association of long non-coding RNA (lncRNA) SNHG1/ miR-195 axis with type 2 diabetes mellitus (T2DM) and islet function.

Methods

The expression of SNHG1 and miR-195 was measured in T2DM patients and in healthy subjects. Correlation between indciators was evaluated using Pearson correlation analysis. INS-1 cells were used to perform the cell function assays. Insulin secretion by INS-1 was detected using ELISA. Cell counting kit-8 (CCK-8) and flow cytometry was used to detect cell proliferation and apoptosis. Luciferase report assay was to used to verify the target of SNHG1.

Results

The expression of SNHG1 was increased and miR-195 level was decreased in the serum of T2DM patients. Both SNHG1 and miR-195 could be biomarkers for T2DM diagnosis. The fasting plasma glucose (FPG) and HbA1c were positively related to SNHG1 and negatively related to miR-195. SNHG1 inhibited insulin secretion, and cell proliferation and promoted apoptosis of INS-1 cells via binding to miR-195.

Conclusions

Detection of SNHG1 and miR-195 might predict T2DM. SNHG1 could suppress proliferation and insulin secretion, but promote apoptosis of INS-1 cells via sponging miR-195.

Peer Review reports

Background

Diabetes is a chronic metabolic disease characterized by hyperglycemia, which has been listed as the third major chronic noninfectious disease that endangers global public health [1, 2]. Since diabetes does not present with obvious symptoms in the initial stage, leading to challenge of early diagnosis [3]. About 90% of diabetic patients belong to type 2 diabetes mellitus (T2DM) [4]. The pathogenesis of T2DM mainly includes insufficient insulin secretion by islet β cells and insulin resistance in peripheral tissues [5]. The progressive decline of islet β-cell function is the core mechanism of the pathogenesis of T2DM and a crucial factor in the progression of the disease [6]. The interaction of environment, diet, genetic factors, and immune factors leads to the disorder and even apoptosis of islet β cells, which leads to insufficient insulin secretion or insulin resistance even glucose metabolism disorder.

Long non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs with a length more than 200 nucleotides. LncRNA can exist stably in serum, and serum lncRNA acts as a predictor in the process of disease diagnosis and treatment [7, 8]. The roles of lncRNAs in T2DM have been widely reported. For example, lncRNA prostaglandin-endoperoxide synthase 2 (PTGS2) is enhanced in serum from T2DM patients and it can regulate the impacts of damaged islet β cells [9]. LncRNA H2A clustered histone 11 (HIST1H2AG-6) and peroxisomal fatty acid beta-oxidation multifunctional protein AIM1 (AIM1-3) both have correlations with T2DM and may act as biomarkers of T2DM [10]. Previous research show that lncRNA may play a role in maintaining islet β cell function and insulin signal transduction, thus have an impact on the occurrence and development of diabetes [11, 12]. Zhang and colleagues find that lncRNA TRAF3IP2 antisense RNA 1 (βFaar) influences islet β-cell function and survival during obesity in mice [13]. It has also been shown that targeting lncRNA neurotrophin 3–5 (NTF3-5) can suppress islet cell apoptosis and oxidative station, and accelerate islet cell proliferation and insulin secretion [14]. LncRNA small nucleolar RNA host gene 1 (SNHG1) is a regulatory factor found in recent years, which is related to the normal physiological activity of cells and the pathological mechanism, and disease development of many cancers [15]. It has been found that the expression of SNHG1 is up-regulated in retinal pigment epithelial cells under the high glucose situation [16]. SNHG1 is an overexpressed lncRNA in subjects with diabetic retinopathy, indicating that long-term high glucose may induce the increased level of SNHG1 [17]. At present, there are few studies on SNHG1 in islet β cells.

LncRNAs can modulate gene expression by binding to the downstream microRNAs (miRNAs). And the role of miRNAs in T2DM has also been reported [18]. Previously, miR-195 is identified to be a candidate target of SNHG1 [19, 20]. Moreover, miR-195 has been determined to be dysregulated in the serum of T2DM patients [21, 22]. Therefore, the involvement of miR-195 in the role of SNHG1 in T2DM attracts our interest. This study detected the expression of SNHG1 and miR-195 in the serum of patients with T2DM, to analyze the relationship between serum SNHG1 or miR-195 and islet function in patients with T2DM, and to research the effect of SNHG1 on islet β-cell apoptosis and its mechanism with the involvement of miR-195.

Methods

Collection of study subjects

Eighty-six newly diagnosed patients with T2DM treated in the endocrinology clinic of Affiliated Hospital of Panzhihua University from January 2021 to March 2022 were volunteers in this research. Inclusion criteria were fasting plasma glucose (FPG) ≥ 7.0 mmol/L and 2-hour blood glucose ≥ 11.1 mmol/L in oral glucose tolerance test (OGTT) [23]. Exclusion criteria were: secondary diabetes; pregnant and lactating women; combined with hyperthyroidism, pancreatic dysfunction, liver dysfunction, and other related diseases that may cause abnormal blood glucose; combined with other endocrine diseases, malignant tumors, autoimmune diseases, or other systemic diseases. Eighty-one healthy physical examinees were recruited, and OGTT was performed on all the control physical examinees. All procedures were approved by the ethics committee of Affiliated Hospital of Panzhihua University (approval number: 2020053), and all the research subjects provided the informed consent form.

In the morning, 4 mL of blood (fasting for 8–12 h) were collected from all subjects and partitioned into RNase-free EP tubes. After routine serum separation, these samples were stored in the refrigerator for subsequent RNA extraction or testing routine biochemical indicators.

Biochemical measurements

Plasma levels of biochemical indicators including fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density–lipoprotein cholesterol (LDL-C), and high density–lipoprotein cholesterol (HDL-C) were detected. HbA1c was determined by high-speed liquid chromatography (Arkray 8160). FPG and blood lipids were measured by immunoturbidimetry (Beckman AU680).

Cell line purchase and transfection

INS-1 cells were purchased from the Cell Institute of Shanghai Academy of Life Sciences which is affiliated with the Chinese Academy of Sciences (China; Catalog No. CBP60939) and treated with RPMI-1640 medium containing volume fraction 10% FBS (11.1 mmol/L glucose, 10 mmol/L HEPES, 50 µmol/L β-mercaptoethanol, 1 mmol/L sodium pyruvate, 100 U/mL penicillin, 100 µg/mL streptomycin) and incubated at 37 °C in a 5% CO2 incubator.

The cells were categorized into negative control group and transfected group. The small interfering (si) RNA targeting SNHG1 (si-SNHG1), SNHG1-overexpressing plasmid (p-SNHG1), miR-195 inhibitor, and its negative control (NC, miR-NC) from Gene Pharm (Shanghai, China) were transfected according to the instructions of Lipofectamine 2000. After 48 h, the cells were utilized for the following experiments.

RNA expression detection

The serum and INS-1 cells were collected for RNA isolation. Trizol LS reagent from the Thermo company (America) was purchased and applied to the exact total RNA. The reverse transcription kit (EnzyArtisan, Shanghai, China) was utilized for cDNA obtainment for SNHG1, and another cDNA synthesis kit (ABSIN, Shanghai, China) for miRNA. The purity of RNA was confirmed and genomic DNA (gDNA) was cleaned with gRNA eraser (Takara, Japan) before the transcription. The SYBR qPCR green kit (Qiagen, Beijing, China) was used for gene expression detection on 7700 systems (Applied Biosystems, CA, America). 2-∆∆CT is the method to calculate the expression of SNHG1 and miR-195 using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and U6 as references, respectively.

ELISA assay

The cells in each group were seeded in the 96-well flat plate for 24 h. Low glucose (3.3 mM) and high glucose (HG, 16.70 mM) were added for 1 h. The insulin secreted into the medium in each group was detected by an insulin ELISA kit (Abcam, UK). The concrete steps were as follows. The cell culture was transferred into the wells coated with insulin antibodies, and a biotinylated anti-insulin antibody was provided. After washing, horseradish peroxidase-conjugated streptavidin was pipetted to the wells and then washed away. The tetramethylbenzidine substrate solution and the stop solution were added in turn, and the intensity was detected at 450 nm.

Cell counting kit-8 (CCK-8) assay

INS-1 cells with a good growth state and confluence rate of 90% were prepared into 5 × 104/mL single cell suspension with complete medium and seeded into 96-well plates (100 µL/well). The cell supernatant was discarded, and the prepared 10% CCK-8 reagent (Fusheng, Shanghai, China) was supplemented to each well with 100 µL at 0 h, 24 h, 48 h, and 72 h. The reagent background well was set and incubated in an incubator at 37℃. After 1 h, the OD value was certified with a microplate reader at 450 nm wavelength.

Flow cytometry assay

PBS solution was mixed with cells and centrifuged at 1000 g for 5 min. The INS-1 cells were suspended with binding buffer solution. 100 µL of cell suspension was sucked, and 5 µL of Annexin V-FITC solution (ThermoFisher, USA) was added and cultured for 15 min. Binding buffer was used to wash the cells. 5 µL of PI dye was supplemented and reacted for 10 min. Cell apoptotic rate was assessed by flow cytometry within 1 h.

Luciferase reporter assay

Bioinformatics (ENCORI) predicted that identical bases might exist in miR-195 and SNHG1. Double luciferase reporter kit (Yeason, Shanghai, China) was utilized to estimate the targeting linkage between miR-195 and SNHG1. Luciferase reporter of SNHG1 was constructed containing wild-type binding sites or mutant binding sites of miR-195, and then co-transfected with miR-195 mimic or inhibitor or miR-NC into INS-1 cells. The luciferase activity was tested 48 h after co-transfection. The fluorescence values of firefly and renilla luciferase were detected by the automatic microplate reader, and the fluorescence value of the renilla luciferase was used as an internal reference.

Statistical analysis

All data were analyzed using SPSS 21.0, expressed by mean and standard deviation (SD). An independent sample t-test was used to compare differences between two groups, while one-way ANOVA with post-hoc testing was utilized to compare differences among multiple groups. Three replicates were set for each experiment. The clinical predictive value of SNHG1 was revealed by the ROC curve. The linear relationship between the two variables was estimated by Pearson’s correlation analysis. The difference was significant when P < 0.05.

Results

Clinical parameters of the subjects

The number of subjects included in both the T2DM and healthy groups were similar in age, sex, BMI (Table 1, P > 0.05). The serological and biochemical indexes of the T2DM and healthy subject groups show that the levels of FPG, HbAlc in the T2DM group were significantly higher (Table 1, P < 0.05) than healthy subjects. No significant differences were detected in TG, TC, HDL-C, and LDL-C levels between the two groups. The findings suggest that T2DM patients had increased fasting blood glucose and impaired islet β-cell function.

Table 1 Clinical parameters of all recruited individuals
Full size table

The level of SNHG1 in T2DM patients

qRT-PCR was performed to certify the level of SNHG1 in all subjects, as exhibited in Fig. 1A. The serum level of SNHG1 in T2DM patients was increased (P < 0.001), suggesting that it might be related to the development of T2DM.

Fig. 1
figure 1

(A) Acceleration of SNHG1 expression in T2DM patients. (B) High accuracy of SNHG1 for T2DM patients was observed. (C) Positive correlation between SNHG1 and FPG in T2DM patients. (D) Interaction between SNHG1 and HbA1c. ***P < 0.001

Full size image

Then ROC curve was plotted to evaluate the diagnostic performance of SNHG1 in T2DM. The AUC of SNHG1 showed that SNHG1 expression was an indicator for screening T2DM from healthy cohort (Fig. 1B, sensitivity = 0.860, specificity = 0.827). The correlation between the expression level of SNHG1 and T2DM of the patients was further analyzed. The results are shown in Fig. 1C and D, Pearson analysis reported that the changes of SNHG1 in the serum of T2DM patients were associated with FPG and HbA1c levels (P < 0.001), documenting the similar tendency of SNHG1 and islet function in patients with T2DM.

Impact of SNHG1 on insulin secretion, proliferation activity, and apoptosis

INS-1 cells express many important features of normal pancreatic islet beta-cells such as insulin secretion, so INS-1 cells were applied for the cell function experiments [24]. As indicated in Fig. 2A, when the si-SNHG1 transfected to the INS-1 cells, the expression of SNHG1 was lessened, while the expression was upregulated when transfected with p-SNHG1 (P < 0.001). The changes in insulin secretion level after 1 h of low glucose and high glucose stimulation were detected, respectively. In Fig. 2B, in the 16.70 mM group, insulin secretion level was lessened after p-SNHG1 stimulation and enhanced after si-SNHG1 transfection (P < 0.001), indicating that p-SNHG1 inhibited insulin secretion, and effectively decreased insulin secretion ability. The cell proliferation level of p-SNHG1 group was decreased than that of control group and was raised in the si-SNHG1 group (Fig. 2C, P < 0.01). In addition to this, the highly expressed SNHG1 improved cell apoptosis, and its silence suppressed cell death rate (Fig. 2D, P < 0.001).

Fig. 2
figure 2

(A) The expression of SNHG1 was increased using p-SNHG1, and decreased using si-SNHG1. (B) Insulin secretion lessened with silencing SNHG1 expression and raised with elevated SNHG1 expression. (C) Augment of SNHG1 prevented INS-1 proliferation and its knockdown exaggerated proliferation. (D) SNHG1 overexpression promoted INS-1 cell apoptosis while its downregualtion suppressed cell apoptosis. ***P < 0.001

Full size image

SNHG1 targets the sequence of miR-195

For mechanism exploration, the downstream targets of SNHG1 were predicted. According to the bioinformatics method, SNHG1 contains the binding site of miR-195 (Fig. 3A). Dual luciferase reporter was carried out to confirm the affinity between SNHG1 and miR-195, and the results are shown in Fig. 3B. The activity of luciferase in INS-1 cells was decreased by cotransfection of miR-195 mimic and wide type of SNHG1 (P < 0.001). Luciferase activity of mutant SNHG1 transfected cells were not impacted by miR-195 expression (Fig. 3B). The results indicated that miR-195 was a target of SNHG1.

Fig. 3
figure 3

(A) Targeted sequences between miR-195 and SNHG1. (B) The luciferase report identified that miR-195 was a target gene of SNHG1. ***P < 0.001

Full size image

Expression and value of miR-195 on T2DM patients

Furthermore, the clinical values of miR-195 in T2DM patients were further examined. The expression of miR-195 in patients with T2DM decreased, indicating its potential role in T2DM (Fig. 4A, P < 0.001). The clinical impact of miR-195 was estimated by the ROC curve, that miR-195 had a certain possibility of acting as a biomarker, serum miR-195 can differentiate T2DM patients from healthy controls with the AUC of 0.896 (Fig. 4B). Additionally, Pearson correlation analysis found that level of miR-195 in T2DM patients were negatively related to the blood lipid levels of FPG and HbA1c which in turn are directly proportional to increase in SNHG1 levels (Fig. 4C-D). All findings determined the important role of miR-195 in the occurrence of T2DM.

Fig. 4
figure 4

(A) MiR-195 expression was decreased in T2DM patients. (B) Predictive value of miR-195 was depicted using ROC curve. (C) The inhibition of miR-195 levels was related to FPG and (D) HbA1c levels. ***P < 0.001

Full size image

MiR-195 acted as a mediated factor of SNHG1

In addition, the role of miR-195 in cell function of INS-1 cells was explored. As displayed in Fig. 5A, silencing SNHG1 could promote the expression of miR-195 (P < 0. 001), suggesting that SNHG1 is a competitive endogenous RNA targeting miR-195. The cotransfection of si-SNHG1 and miR-195 inhibitor decreased the miR-195 levels (Fig. 5A, P < 0.001).

Fig. 5
figure 5

(A) The expression of miR-195 elevated in the si-SNHG1 group, which was reversed by the miR-195 inhibitors. (B–D) SNHG1 modulated insulin secretion, cell proliferation, and apoptotic rate via sponging miR-195. ***P < 0.001, compared to control cells; #P < 0.05, ##P < 0.01, ###P < 0.001, compared to si-SNHG1 group

Full size image

With the incubation of 16.70 mM glucose, the insulin secretion declined in p-SNHG1 group, the trend was opposite to that of si-SNHG1 + miR-195 group (Fig. 5B, P < 0.001). Increasing the expression of miR-195 could improve the INS-1 cell proliferation and alleviate the death of INS-1 cells. The overexpression of miR-195 reversed this tendency, suggesting that SNHG1 affects the proliferation and apoptosis of INS-1 cells by controlling the expression of miR-195 (Fig. 5C-D, P < 0.05).

Discussion

T2DM is an endocrine disorder characterized by chronic hyperglycemia caused by a variety of causes [25]. Developing new diagnoses and treatment schemes is important to control the occurrence and development of T2DM [26]. T2DM is the most prevalent type of diabetes, which is the abnormal increase of blood glucose induced by insulin resistance [27]. Its main clinical characteristics are insulin resistance, pancreatic β-cell secretion dysfunction, blood glucose metabolism disorder, etc [28]. LncRNA is correlated with different stages of diabetes, especially in the regulation of diabetic complications such as retinopathy, cardiomyopathy, and non-alcoholic steatohepatitis [29]. The high expression of LINC-PINT may inhibit the occurrence of retinopathy in patients with T2DM [30]. High expression of lncRNA HOTAIR may predict the aggression of T2DM development [31]. LncRNA has become the focus of biomarker and targeted therapy for diabetes.

In this study, it was found that the expression of SNHG1 in the serum of patients with T2DM was raised, indicating the close association of SNHG1 with T2DM. Moreover, elevated expression of SNHG1 was positively correlated with FPG and HbA1c in T2DM patients. The increased expression of SNHG1 may be related to the decrease in islet β cell function. He et al. have also reported that SNHG1 is overexpressed in diabetic retinopathy, a complication of T2DM [17]. INS-1 cells express many important features of normal pancreatic islet beta-cells, and thus provide a popular model for studying diabetes-related pathological changes of beta-cells in the islets of Langerhans [24]. Therefore, INS-1 cells were applied for the cell function experiments. It was found that SNHG1 could inhibit the proliferation of INS-1 cells and accelerate apoptosis, thus suppressing insulin secretion.

Competing endogenous RNA (ceRNA) is one of the most essential functional mechanisms of lncRNA. LncRNA can regulate gene expression by sponging miRNAs [32]. Therefore, the target gene of SNHG1 was predicted to investigate the underlying regulatory mechanism. Based on the bioinformatic prediction and luciferase reporter assay, miR-195 was identified to be a target gene of SNHG1. Consistently, Articles by Ji et al. and Chen et al. also report the target relationship between SNHG1 and miR-195 [20, 33]. Publications have confirmed that miRNA is involved in regulating diabetes mellitus, which may be related to the process of insulin synthesis and secretion [34, 35]. A variety of dysregulated miRNAs have been identified in T2DM patients, which may become markers to predict the onset of T2DM or evaluate the disease progression [36]. The present study verified that miR-195 had low expression in T2DM patients and it could differentiate T2DM patients from healthy humans. The lessened expression of miR-195 was correlated to the elevated FPG and HbA1c levels. Consistently, miR-195 is decreased in the plasma of patients with T2DM in a previous observation [37]. These results indicated that miR-195 might be implicated in the occurrence and progression of T2DM.

Early studies have found that a variety of miRNAs are abundant in islet β-cells and can affect insulin secretion by participating in the regulation of islet β-cell proliferation and insulin synthesis and secretion [38]. In this study, SNHG1 knockdown led to the elevation of miR-195 expression, accompanied with secretion of insulin, but this trend was ameliorated by the inhibition of miR-195 expression, suggesting SNHG1 might moderate insulin production via miR-195. In addition, silencing SNHG1 could significantly promote the proliferation ability and suppress the apoptosis of islet β cells, while miR-195 downregulation could reduce the function si-SNHG1, indicating that miR-195 was involved in the regulatory role of SNHG1 in the proliferation and apoptosis of INS-1 cells. Previously, Ortega et al. identify that the expression of miR-195 is diminished in patients with T2DM [37]. High levels of FBG may contribute to the decreased expression of miR-195 [21]. Another publication indicates that miR-195 is reduced in rat models with diabetic nephropathy and it regulates the ability of macrophages [39]. Taken together, SNHG1 might regulate proliferation and apoptosis of INS-1 cells by controlling the level of miR-195, resulting in decreased insulin secretion.

Conclusions

In conclusion, elevated SNHG1 and decreased miR-195 expression were correlated with high FPG and HbA1c levels and might differentiate T2DM patients from healthy humans. SNHG1 could suppress proliferation and insulin secretion of INS-1 cells, but promote cell apoptosis, which was reversed by miR-195. Although the present findings presented the pivotal role of SNHG1/miR-195 in T2DM based on in vitro experiments, the function should be verified in vivo experiments. In addition, the underlying mechanism needs further exploration, and the downstream target of miR-195 should be determined, and their interaction in T2DM can be explored both in vivo and in vitro. Moreover, the underlying pathways should also be investigated in future studies.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

FPG:

Fasting plasma glucose

gDNA:

Genomic DNA

OGTT:

Oral glucose tolerance test

T2DM:

Type 2 diabetes mellitus

References

  1. Malo J, Alam MJ, Islam S, Mottalib MA, Rocki MMH, Barmon G, Tinni SA, Barman SK, Sarker T, Khan MNI et al. Intestinal alkaline phosphatase deficiency increases the risk of diabetes. BMJ open Diabetes Res care 2022, 10(1).

  2. Zheng F, Liu S, Liu Y, Deng L. Effects of an Outpatient Diabetes Self-Management Education on Patients with Type 2 Diabetes in China: A Randomized Controlled Trial. Journal of diabetes research 2019, 2019:1073131.

  3. Liu S, Gao Y, Shen Y, Zhang M, Li J, Sun P. Application of three statistical models for predicting the risk of diabetes. BMC Endocr Disorders. 2019;19(1):126.

    Article  CAS  Google Scholar 

  4. Doostkam A, Fathalipour M, Anbardar MH, Purkhosrow A, Mirkhani H. Therapeutic Effects of Milk Thistle (Silybum marianum L.) and Artichoke (Cynara scolymus L.) on Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Rats. Canadian journal of gastroenterology & hepatology 2022, 2022:2868904.

  5. Okamoto A, Yokokawa H, Nagamine T, Fukuda H, Hisaoka T, Naito T. Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists. J Diabetes Metab Disord. 2021;20(2):2121–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Leng Y, Zhou X, Xie Z, Hu Z, Gao H, Liu X, Xie H, Fu X, Xie C. Efficacy and safety of Chinese herbal medicine on blood glucose fluctuations in patients with type 2 diabetes mellitus: a protocol of systematic review and meta-analysis. Medicine. 2020;99(34):e21904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhao C, Hu J, Wang Z, Cao ZY, Wang L. Serum LncRNA PANDAR may act as a novel serum biomarker of Diabetic Nephropathy in patients with type 2 diabetes. Clin Lab 2020, 66(6).

  8. Li M, Zhao Y, Li H, Deng X, Sheng M. Application value of circulating LncRNA in diagnosis, treatment, and prognosis of breast cancer. Funct Integr Genomics. 2023;23(1):61.

    Article  CAS  PubMed  Google Scholar 

  9. Chen Q, He Y, Wang X, Zhu Y, Huang Y, Cao J, Yan R. LncRNA PTGS2 regulates islet β-cell function through the miR-146a-5p/RBP4 axis and its diagnostic value in type 2 diabetes mellitus. Am J Translational Res. 2021;13(10):11316–28.

    CAS  Google Scholar 

  10. Jiang H, Lou P, Chen X, Wu C, Shao S. Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes. BMC Med Genom. 2021;14(1):149.

    Article  CAS  Google Scholar 

  11. Wong WKM, Sørensen AE, Joglekar MV, Hardikar AA, Dalgaard LT. Non-coding RNA in pancreas and β-Cell development. Non-coding RNA 2018, 4(4).

  12. López-Noriega L, Rutter GA. Long non-coding RNAs as key modulators of pancreatic β-Cell Mass and function. Front Endocrinol. 2020;11:610213.

    Article  Google Scholar 

  13. Zhang F, Yang Y, Chen X, Liu Y, Hu Q, Huang B, Liu Y, Pan Y, Zhang Y, Liu D, et al. The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice. Nat Commun. 2021;12(1):3997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang XL, Zhang Y, Zhu HQ, Zhang CY, Jiao JS, Xing XY. Regulation of Lnc-NTF3-5 on islet β-cell dysfunction in high glucose environment and related mechanisms. Eur Rev Med Pharmacol Sci. 2019;23(23):10501–8.

    PubMed  Google Scholar 

  15. Chen Y, Li Z, Chen X, Zhang S. Long non-coding RNAs: from disease code to drug role. Acta Pharm Sinica B. 2021;11(2):340–54.

    Article  CAS  Google Scholar 

  16. Yang J, Yang K, Meng X, Liu P, Fu Y, Wang Y. Silenced SNHG1 inhibited epithelial-mesenchymal transition and inflammatory response of ARPE-19 cells Induced by High glucose. J Inflamm Res. 2021;14:1563–73.

    Article  PubMed  PubMed Central  Google Scholar 

  17. He FT, Fu XL, Li MH, Fu CY, Chen JZ. LncRNA SNHG1 targets miR-340-5p/PIK3CA axis to regulate microvascular endothelial cell proliferation, migration, and angiogenesis in DR. Kaohsiung J Med Sci. 2023;39(1):16–25.

    Article  CAS  PubMed  Google Scholar 

  18. Shahrokhi SZ, Saeidi L, Sadatamini M, Jafarzadeh M, Rahimipour A, Kazerouni F. Can Mir-145-5p be used as a marker in diabetic patients? Arch Physiol Biochem. 2022;128(5):1175–80.

    Article  CAS  PubMed  Google Scholar 

  19. Bai J, Xu J, Zhao J, Zhang R. lncRNA SNHG1 cooperated with miR-497/miR-195-5p to modify epithelial-mesenchymal transition underlying colorectal cancer exacerbation. J Cell Physiol. 2020;235(2):1453–68.

    Article  CAS  PubMed  Google Scholar 

  20. Ji YY, Meng M, Miao Y. lncRNA SNHG1 promotes progression of Cervical Cancer through miR-195/NEK2 Axis. Cancer Manag Res. 2020;12:11423–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hu Y, Li Q, Zhang L, Zhong L, Gu M, He B, Qu Q, Lao Y, Gu K, Zheng B, et al. Serum mir-195-5p exhibits clinical significance in the diagnosis of essential hypertension with type 2 diabetes Mellitus by Targeting DRD1. Clin (Sao Paulo). 2021;76:e2502.

    Article  Google Scholar 

  22. Li Y, Yang J, Tao W, Yang M, Wang X, Lu T, Li C, Yang Y, Yao Y. The single nucleotide polymorphisms (rs1292037 and rs13137) in miR-21 were Associated with T2DM in a Chinese Population. Diabetes Metab Syndr Obes. 2022;15:189–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang LK, Wang H, Wu XL, Shi L, Yang RM, Wang YC. Relationships among resistin, adiponectin, and leptin and microvascular complications in patients with type 2 diabetes mellitus. J Int Med Res. 2020;48(4):300060519870407.

    Article  CAS  PubMed  Google Scholar 

  24. Lv X, Zhao Y, Yang X, Han H, Ge Y, Zhang M, Zhang H, Zhang M, Chen L. Berberine Potentiates insulin secretion and prevents β-cell dysfunction through the miR-204/SIRT1 signaling pathway. Front Pharmacol. 2021;12:720866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu Z, Qu CY, Li JX, Wang YF, Li W, Wang CZ, Wang DS, Song J, Sun GZ, Yuan CS. Hypoglycemic and Hypolipidemic effects of Malonyl Ginsenosides from American Ginseng (Panax quinquefolius L.) on type 2 Diabetic mice. ACS Omega. 2021;6(49):33652–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhou W, Ye SD, Chen C, Wang W. Involvement of RBP4 in Diabetic Atherosclerosis and the role of vitamin D intervention. J Diabetes Res. 2018;2018:7329861.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Amoani B, Sakyi SA, Mantey R, Laing EF, Ephraim RD, Sarfo-Katanka O, Koffie S, Obese E, Afranie BO. Increased metformin dosage suppresses pro-inflammatory cytokine levels in systemic circulation and might contribute to its beneficial effects. J Immunoassay Immunochem. 2021;42(3):252–64.

    Article  CAS  PubMed  Google Scholar 

  28. Bai Y, Mo K, Wang G, Chen W, Zhang W, Guo Y, Sun Z. Intervention of Gastrodin in type 2 diabetes Mellitus and its mechanism. Front Pharmacol. 2021;12:710722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Abdulle LE, Hao JL, Pant OP, Liu XF, Zhou DD, Gao Y, Suwal A, Lu CW. MALAT1 as a diagnostic and therapeutic target in diabetes-related complications: a Promising Long-Noncoding RNA. Int J Med Sci. 2019;16(4):548–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zha T, Su F, Liu X, Yang C, Liu L. Role of long non-coding RNA (LncRNA) LINC-PINT downregulation in Cardiomyopathy and Retinopathy Progression among patients with type 2 diabetes. Med Sci Monitor: Int Med J Experimental Clin Res. 2019;25:8509–14.

    Article  CAS  Google Scholar 

  31. Wang H, Xia Y, Zhang Y. Diagnostic significance of serum lncRNA HOTAIR and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2021;13(1):97.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Xu S, Dong H, Zhao Y, Feng W. Differential expression of long non-coding RNAs and their role in Rodent Neuropathic Pain models. J pain Res. 2021;14:3935–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen Y, Sheng HG, Deng FM, Cai LL. Downregulation of the long noncoding RNA SNHG1 inhibits tumor cell migration and invasion by sponging miR-195 through targeting Cdc42 in oesophageal cancer. Kaohsiung J Med Sci. 2021;37(3):181–91.

    Article  CAS  PubMed  Google Scholar 

  34. Lu Z, Wang J, Wang X, Li Z, Niu D, Wang M, Xiang J, Yue Y, Xia Y, Li X. miR-375 Promotes Pancreatic Differentiation In Vitro by Affecting Different Target Genes at Different Stages. Stem cells international 2021, 2021:6642983.

  35. Xu H, Zhao B, Zhong W, Teng P, Qiao H. Identification of miRNA signature Associated with Erectile Dysfunction in type 2 diabetes Mellitus by Support Vector Machine-recursive feature elimination. Front Genet. 2021;12:762136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. He X, Kuang G, Wu Y, Ou C. Emerging roles of exosomal miRNAs in diabetes mellitus. Clin Translational Med. 2021;11(6):e468.

    Article  CAS  Google Scholar 

  37. Ortega FJ, Mercader JM, Moreno-Navarrete JM, Rovira O, Guerra E, Esteve E, Xifra G, Martínez C, Ricart W, Rieusset J, et al. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care. 2014;37(5):1375–83.

    Article  CAS  PubMed  Google Scholar 

  38. Sun X, Ji G, Li P, Li W, Li J, Zhu L. Mir-344-5p modulates cholesterol-Induced β-Cell apoptosis and dysfunction through regulating Caveolin-1 expression. Front Endocrinol. 2021;12:695164.

    Article  Google Scholar 

  39. Zhu LL, Wang HY, Tang T. Effects of miR-195 on diabetic nephropathy rats through targeting TLR4 and blocking NF-κB pathway. Eur Rev Med Pharmacol Sci. 2021;25(3):1522–9.

    PubMed  Google Scholar 

Download references

Acknowledgements

NA.

Funding

No funding was received for conducting this study.

Author information

Author notes

  1. Tianxiang Xu and Tuwang Shen contributed equally to this work.

Authors and Affiliations

  1. Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530001, China

    Tianxiang Xu

  2. Operating Room, North China University of Science and Technology Affiliated Hospital, Tangshan, 063000, China

    Tuwang Shen

  3. Department of General Practice, Hefei First People’s Hospital, Hefei, 230031, China

    Song Yang

  4. Department of General Practice, Affiliated Hospital of Panzhihua University, 27 Taoyuan Street, Panzhihua, Sichuan, 617200, China

    Yuan Li & Li Liu

  5. Department of Clinical Laboratory, Huangshi Central Hospital, No. 35, Shengming Road, Jinshan Street, Tieshan District, Development Zone, Huangshi, Hubei, 435000, China

    Lili Du

  6. Huangshi Tumor Molecular Diagnosis and Treatment Key Laboratory, Huangshi, 435000, China

    Lili Du

Authors
  1. Tianxiang Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Tuwang Shen
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Song Yang
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Yuan Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Li Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Lili Du
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

TXX, TWS, SY, LL and YL made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data, and draft of the manuscript. LL and LLD revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Li Liu or Lili Du.

Ethics declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All procedures were approved by the ethics committee of Affiliated Hospital of Panzhihua University, and all the research subjects provided the informed consent form.

Consent for publication

NA.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, T., Shen, T., Yang, S. et al. Clinical significance of circulating long non-coding RNA SNHG1 in type 2 diabetes mellitus and its association with cell proliferation of pancreatic β-cell. BMC Endocr Disord 24, 225 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12902-024-01755-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12902-024-01755-6

Keywords

BMC Endocrine Disorders

ISSN: 1472-6823

Contact us