Overexpression of microRNA-2l6a inhibits autophagy by targeting regulated MAP1S in colorectal cancer
Background: Autophagy executes the rapid degradation of unneeded proteins and organelles through the lysosomal pathway, and is a crucial catabolic process widely conserved among eukaryotes. miRNAs can modulate autophagy by targeting genes encoding proteins involved in the process. A great deal of re...
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Published in | OncoTargets and therapy p. 4621 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Dove Medical Press Limited
01.06.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Background: Autophagy executes the rapid degradation of unneeded proteins and organelles through the lysosomal pathway, and is a crucial catabolic process widely conserved among eukaryotes. miRNAs can modulate autophagy by targeting genes encoding proteins involved in the process. A great deal of researchhas indicated that miR-216a was a functional miRNA related to tumorigenesis. However, the contribution of miR-216a to autophagy in colorectal cancer (CRC) remains unclear. The purpose of this study was to investigate the role of miR-216a in autophagy in CRC cells. Methods: The expression levels of miR-216a in 67 paired CRC patients were evaluated by qRT-PCR. Direct gene targeting predicted by TargetScan and miRanda was confirmed by luciferase activity. Western blot and flow cytometry were used to identify the regulatory mechanism of miR-216a on autophagy in CRC cells. Results: We determined that miR-216a is downregulated in CRC by screening its expression in 67 CRC tissue samples. Dual luciferase reporter assays showed that miR-216a binds the 3'-UTR of MAP1S, suggesting that MAP1S is a direct target of miR-216a. miR-216a could inhibit autophagy in HCT-116 and HT-29 CRC cells through downregulating MAP1S expression. Flow cytometry and Western blot analysis demonstrated that overexpression of miR-216a reduced MAP1S mRNA and protein levels. Moreover, we determined that miR-216a-regulated inhibition of autophagy via MAP1S regulation involves the TGF-[beta] pathway. Conclusion: Taken together, our findings indicate that miR-216a was a tumor-suppressor miRNA in human CRC, which can inhibit autophagy via the TGF-[beta]/MAP1S pathway. Keywords: miR-216a, MAP1S, autophagy, TGF-[beta], colorectal cancer |
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ISSN: | 1178-6930 1178-6930 |
DOI: | 10.2147/OTT.S196992 |