Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function

Abstract

Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose-stimulated insulin secretion, and enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full-length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196-122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet β-cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes.

Long Noncoding RNA GUSBP3 And SAM4 Function As Potential Diagnostic Biomarkers of Type 2 Diabetes Mellitus In Kazak Populations In The Xinjiang Region of China

“…reported that lncRNA uc.322 was associated with FIns, and that lncRNA uc.322 upregulation in pancreatic β-cells increased the expression of insulin transcription factors and promoted insulin secretion [19]. In addition, dysregulation of lncRNAs has been associated with the development of complications such as diabetic nephropathy [20], which may account for the association of lnc-GUSBP3 with Cr and UA.…”

Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes

“…Transcriptomic profiling of the human islets also found LOC283177 is co-expressed with the insulin synthesis and secretion regulators, including MAP-kinase activating death domain (MADD), synaptotagmin 11 (SYT11), and paired box 6 (PAX6) [76]. Besides that, lncRNA uc.322 is also exclusively expressed in pancreatic β-cells [55]. Overexpression of lncRNA uc.322 in the MIN6 cells caused greater glucose-stimulated insulin secretion via the upregulations of the PDX1 and forkhead box O1 (FOXO1) expressions [55].…”

“…Besides that, lncRNA uc.322 is also exclusively expressed in pancreatic β-cells [55]. Overexpression of lncRNA uc.322 in the MIN6 cells caused greater glucose-stimulated insulin secretion via the upregulations of the PDX1 and forkhead box O1 (FOXO1) expressions [55]. Another lncRNA is the long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT), that may regulate insulin synthesis and secretion, and this lncRNA expression was reduced in the T2D mouse model [51] and plasma of T2D patients [77].…”

Long noncoding RNAs in cardiometabolic disorders

“…Knockdown of TUG1 induces apoptosis of and decreases insulin secretion in β‐cells in vitro and in vivo [81]. lncRNA ultraconserved 322 ( uc.322 ) is also highly expressed in pancreatic tissue, where it induces the expression of the insulin transcription factors PDX1 , and thereby promoting insulin secretion [82]. LncRNA myocardial infarction associated transcript ( MIAT ) or Gomafu , a nuclear‐enriched lncRNA, promotes hepatic insulin resistance by acting as a miR‐139 sponge and de‐represses the expression of its target gene FoxO1 , which plays an important role in gluconeogenesis and glucose production in hepatocytes [83].…”