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Long noncoding RNA myocardial infarction–associated transcript regulated the pancreatic stellate cell activation to promote the fibrosis process of chronic pancreatitis
Author(s) -
Liu Hao,
Yu Kaihuan,
Ma Peng,
Xiong Liangkun,
Wang Maoming,
Wang Weixing
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28231
Subject(s) - pancreatitis , long non coding rna , hepatic stellate cell , non coding rna , rna , myocardial infarction , fibrosis , cancer research , medicine , microbiology and biotechnology , biology , gene , genetics
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.