Long noncoding RNA myocardial infarction–associated transcript regulated the pancreatic stellate cell activation to promote the fibrosis process of chronic pancreatitis. Issue 6 (23rd December 2018)

• Record Type: Journal Article
• Authors: Liu, Hao; Yu, Kaihuan; Ma, Peng; Xiong, Liangkun; Wang, Maoming; Wang, Weixing
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 6(2019)
• Page Start: 9547
• Page End: 9555
• Publication Date: 2018-12-23
• Subjects: chronic pancreatitis -- human pancreatic stellate cells -- long noncoding RNA -- myocardial infarction–associated transcript; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28231
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Background: Long noncoding RNAs (lncRNAs) play crucial roles in fibrosis process. In our previous RNA‐seq study, we found that lncRNA myocardial infarction–associated transcript (MIAT) was differentially expressed in pancreatic tissues of chronic pancreatitis (CP) patients. However, the function of MIAT in CP remains unknown. This study was aimed to investigate the function and underlying mechanism of MIAT in pancreatic fibrosis. Materials and Methods: The expression levels of MIAT, miR‐216a‐3p, cyclooxygenase 2 (COX‐2), α‐smooth muscle actin (α‐SMA), and collagen I were estimated by Western blot analysis and qualitative reverse transcription polymerase chain reaction. The relationships between miR‐216a‐3p, MIAT, and COX‐2 were confirmed by luciferase reporter assay. The proliferation of human pancreatic stellate cells (HPaSteCs) was detected by cell counting kit‐8 assay. Results: We found that MIAT, along with the levels of fibrosis‐related proteins α‐SMA and collagen I, as well as COX‐2 were upregulated, while miR‐216a‐3p was downregulated in transforming growth factor (TGF)‐β1‐stimulated HPaSteCs. Mechanistically, MIAT acted as a molecular sponge for miR‐216a‐3p. Furthermore, we identified COX‐2 as a direct target of miR‐126a‐3p. Additionally, MIAT overturned the inhibitory effect of miR‐216a‐3p overexpression and COX‐2 knockdown on the activation and proliferation of HPaSteCs. Conclusion: Our study provided mechanistic insights into a critical role for MIAT as a miRNA sponge in CP. Abstract : Our data demonstrated that myocardial infarction–associated transcript contributed to PSC activation, at least in part, through suppressing miR‐216a‐3p‐mediated COX‐2, thereby leading to pancreatic fibrosis. This finding provides us with a wider understanding of the pathogenesis of CP and novel therapeutic strategies for its treatment.