Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells

Jin, Feiyan; Wang, Ning; Zhu, Yanan; You, Lianghui; Wang, Lintao; De, Wei; Tang, Wei

doi:10.1159/000484191

Cited by 59 publications

(46 citation statements)

References 31 publications

(34 reference statements)

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“…Long noncoding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides [6] that were previously considered “transcription noise”, but studies have increasingly demonstrated that lncRNA transcripts are widely involved in almost every aspect of cellular biological functions, such as cell proliferation [7, 8], differentiation [9, 10], metabolism [11], and apoptosis [12]. Accumulating evidence suggests that the aberrant expression of lncRNAs plays an important role in the regulation of pancreatic β-cell function.…”

Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

Ruan¹,

Lin²,

Ma³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The islet is an important endocrine organ to secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. Long noncoding RNAs (lncRNAs) are involved in a variety of biological functions and play key roles in many diseases, including type 2 diabetes (T2D). The aim of this study was to determine whether lncRNA-p3134 is associated with glucose metabolism and insulin signaling in pancreatic β cells. Methods: LncRNA microarray technology was used to identify the differentially expressed circulating lncRNAs in T2D patients. RT-PCR analyses were performed to determine the expression of lncRNA-p3134 in 30 pairs of diabetic and non-diabetic patients. The correlation of lncRNA-p3134 to clinical data from T2D patients was analyzed. LncRNA-p3134 was overexpressed in Min6 cells and db/db mice by adenovirus-mediated technology. CCK-8, TUNEL, Western blot, glucose-stimulated insulin secretion (GSIS), ELISAs and immunochemistry were performed to determine the effect of lncRNA-p3134 on proliferation, apoptosis and insulin secretion both in vitro and vivo. Results: The circulating level of lncRNA-p3134 was higher in diabetic patients than in non-diabetic controls and was correlated with fasting blood glucose and HOMA-β levels. The lncRNA-p3134 had risen by 4 times in serum exosomes but nearly unchanged in exosome-free samples. The secretion of lncRNA-p3134 was dynamically modulated by glucose in both Min6 cells and isolated mouse islet cells. LncRNA-p3134 positively regulate GSIS through promoting of key regulators (Pdx-1, MafA, GLUT2 and Tcf7l2) in β cells. In addition, the overexpression of lncRNA-p3134 resulted in a decreased apoptosis ratio and partially reversed the glucotoxicity effects on GSIS function in Min6 cells. The restoration of insulin synthesis and secretion the increase of the insulin positive cells areas by upregulation of lncRNA-p3134 in db/db mice confirmed the compensatory role of lncRNA-p3134 to preserve β-cell function. Furthermore, a protective effect of lncRNA-p3134 on GSIS by positive modulation of PI3K/Akt/mTOR signaling was also confirmed. After blocking the PI3K/AKT signals with their specific inhibitor, the effect of overexpressed lncRNA-p3134 on insulin secretion was obviously attenuated. Conclusion: Taken together, the results of this study provide new insights into lncRNA-p3134 regulation in pancreatic β cells and provide a better understanding of novel mechanism of glucose homeostasis.

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Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

Ruan¹,

Lin²,

Ma³

et al. 2018

Cell Physiol Biochem

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“…In tumors, abnormal expression of lncRNAs contributes to the development and progression of cancer by influencing proliferation, apoptosis, autophagy, metastasis, self-renewal, and survival via epigenetic, transcriptional, and post-transcriptional gene regulatory mechanisms [10][11][12]. Furthermore, aberrant expression of lncRNAs can be detected in circulating cancer cells and in the serum and urine of cancer patients, which suggests that lncRNAs may serve as an effective biomarker for cancer detection and prognosis [13,14].…”

Section: Introductionmentioning

confidence: 99%

Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Cui¹,

Yi²,

Xuan³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Maternally expressed gene 3 (MEG3) is an imprinted gene with maternal expression, which may function as a tumor suppressor by inhibiting angiogenesis. To identify the prognostic value of MEG3 in breast cancer, systematic analysis was performed in this study. Methods: To evaluate gene alteration during breast carcinogenesis, we explored MEG3 expression using the Serial Analysis of Gene Expression Genie suite and Oncomine analysis. The prognostic roles of MEG3 in breast cancer were investigated using the PrognoScan database. The heat map and methylation status of MEG3 were determined using the UCSC Genome Browser. Results: We found that MEG3 was more frequently downregulated in breast cancer than in normal tissues and this correlated with prognosis. However, estrogen receptor and progesterone receptor status were found to be positively correlated with MEG3 expression. Conversely, basal-like status, triple-negative breast cancer status, and Scarff Bloom & Richardson grade criterion were negatively correlated with MEG3 expression. Following data mining in multiple big data databases, we confirmed a positive correlation between MEG3 and heparan sulfate proteoglycan 2 (HSPG2) expression in breast cancer tissues. Conclusion: MEG3 could be adopted as a marker to predict the prognosis of breast cancer with HSPG2. However, large-scale and comprehensive research is needed to clarify our results.

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“…10 Research have shown that lncRNAs play a significant role in many life activities, such as dose-compensating effects, 11 epigenetic regulation, 12 regulation of cell cycle, 13 and regulation of cell differentiation 14 and has become a focus of genetic research. 10 Research have shown that lncRNAs play a significant role in many life activities, such as dose-compensating effects, 11 epigenetic regulation, 12 regulation of cell cycle, 13 and regulation of cell differentiation 14 and has become a focus of genetic research.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1

Shi

et al. 2018

J of Cellular Biochemistry

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Long noncoding RNAs (lncRNAs) have been reported to take part in intracellular RNA regulatory networks and play important roles in a lot of pathological processes. Currently, lncRNA X‐inactive specific transcript (XIST) has been proved to regulate cell migration, proliferation, and apoptosis in a series of cancers. In this study, we explored whether XIST can affect cell proliferation, migration, and apoptosis in bladder cancer. The influences of XIST on the cell proliferation, cell cycle, and apoptosis were detected in bladder cancer cells. The effect of XIST on the migration of bladder cancer cells was examined by cell migration assay. Through RNA immunoprecipitation and chromatin immunoprecipitation assays, the binding relationship between XIST and TET1 and the regulatory mechanism of TET1 on p53 were examined. Western blot was performed to detect p53 after knockdown or overexpression of XIST. We found that knockdown of XIST suppressed cell migration and proliferation in vitro. Mechanistically, we confirmed that lncRNA XIST participates in bladder cancer by downregulating p53 via binding to TET1. In conclusion, our research revealed the potential role of XIST‐TET1‐p53 regulatory network in bladder cancer.

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Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells

Cited by 59 publications

References 31 publications

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1

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