DNA methylation-mediated repression of miR-181a/135a/302c expression promotes the microsatellite-unstable colorectal cancer development and 5-FU resistance via targeting PLAG1. (20th April 2018)

• Record Type: Journal Article
• Authors: Shi, Lu; Li, Xiang; Wu, Zhiqiang; Li, Xiaolei; Nie, Jing; Guo, Mingzhou; Mei, Qian; Han, Weidong
• Is Part Of: Journal of genetics and genomics. Volume 45:Number 4(2018)
• Page Start: 205
• Page End: 214
• Publication Date: 2018-04-20
• Subjects: Colorectal cancer -- Microsatellite instability -- microRNA -- PLAG1 -- Chemoresistance -- 5-FU; CRC colorectal cancer -- IGF2 insulin-like growth factor 2 -- miRNA microRNA -- MSI microsatellite instability -- MSS microsatellite stable -- PLAG1 pleomorphic adenoma gene 1 -- 5-FU 5-fluorouracil; Genetics -- Periodicals; Genomics -- Periodicals; 576.505
• DOI: 10.1016/j.jgg.2018.04.003
• Languages: English
• ISSNs: 1673-8527

Abstract

Abstract: Microsatellite instability (MSI) defines a subtype of colorectal cancer (CRC) with typical clinicopathologic characteristics. CRCs with MSI (MSI CRCs) frequently acquire accelerated carcinogenesis and 5-FU resistance, and the exact underlying mechanism remains incompletely understood. Our previous study has identified the microRNA (miRNA) expression profile in MSI CRCs. In this study, three miRNAs (miR-181a, miR-135a and miR-302c) were validated by qRT-PCR to be dramatically decreased in 67 CRC samples. Proliferation and apoptosis assays demonstrated that miR-181a/135a/302c function as tumor suppressors via repressing PLAG1/IGF2 signaling. Moreover, we presented compelling evidence that restoration of miR-181a/135a/302c expression promoted sensitivity of MSI CRC cells to 5-FU treatment. miR-181a/135a/302c exerted their effect on chemoresistance through attenuating PLAG1 expression. Notably, the hypermethylation status of MSI CRC accounts for the decrements of miR-181a/135a/302c. Our results contribute to a better understanding of the mechanism of chemoresistance in MSI CRCs, and provide a clue for digging the biomarkers and therapeutic targets for CRC patients.