Micro sate Hite 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 resista...Micro sate Hite 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-181 a, miR-135 a and miR-302 c） were validated by qRT-PCR to be dramatically decreased in 67 CRC samples. Proliferation and apoptosis assays demonstrated that miR-181 a/135 a/302 c function as tumor suppressors via repressing PLAG1/IGF2 signaling. Moreover, we presented compelling evidence that restoration of miR-181 a/135 a/302 c expression promoted sensitivity of MSI CRC cells to 5-FU treatment. miR-181 a/135 a/302 c exerted their effect on chemoresistance through attenuating PLAG1 expression. Notably, the hypermethylation status of MSI CRC accounts for the decrements of miR-181 a/135 a/302 c. Our results contribute to a better understanding of the mechanism of chemo？resistance in MSI CRCs, and provide a clue for digging the bio markers and therapeutic targets for CRC patients.展开更多
基金supported by the National Key Research and Development Program of China (2016YFC1303501 and 2016YFC1303504)the National Natural Science Foundation of China (Nos. 81572914 and 81230061)
文摘Micro sate Hite 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-181 a, miR-135 a and miR-302 c） were validated by qRT-PCR to be dramatically decreased in 67 CRC samples. Proliferation and apoptosis assays demonstrated that miR-181 a/135 a/302 c function as tumor suppressors via repressing PLAG1/IGF2 signaling. Moreover, we presented compelling evidence that restoration of miR-181 a/135 a/302 c expression promoted sensitivity of MSI CRC cells to 5-FU treatment. miR-181 a/135 a/302 c exerted their effect on chemoresistance through attenuating PLAG1 expression. Notably, the hypermethylation status of MSI CRC accounts for the decrements of miR-181 a/135 a/302 c. Our results contribute to a better understanding of the mechanism of chemo？resistance in MSI CRCs, and provide a clue for digging the bio markers and therapeutic targets for CRC patients.
