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

Lu Shi^{a, #},
Xiang Li^{a, #},
Zhiqiang Wu^a,
Xiaolei Li^a,
Jing Nie^a,
Mingzhou Guo^b,
Qian Mei^{a
, ,},
Weidong Han^{a
, ,}

a.
Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing 100086, China
b.
Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100086, China

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Corresponding author: E-mail address: meiqnn@hotmail.com (Qian Mei); E-mail address: hanwdrsw69@yahoo.com (Weidong Han)

These authors contributed equally to this study.

摘要

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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.
- Colorectal cancer /
- Microsatellite instability /
- microRNA /
- Chemoresistance /
- 5-FU
These authors contributed equally to this study.
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doi: 10.1016/j.jgg.2018.04.003

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

Corresponding author: E-mail address: meiqnn@hotmail.com (Qian Mei); E-mail address: hanwdrsw69@yahoo.com (Weidong Han)

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doi: 10.1016/j.jgg.2018.04.003

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

Corresponding author: E-mail address: meiqnn@hotmail.com (Qian Mei); E-mail address: hanwdrsw69@yahoo.com (Weidong Han)

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