Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 119, Issue 2, Pages 2124-2134Publisher
WILEY
DOI: 10.1002/jcb.26374
Keywords
CRC; GSK-3; miR-377-3p; miRNA; NF-B
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Funding
- China Postdoctoral Science Foundation [2015M581307]
- National Natural Science Foundation of China [31270818, 81572790, 81602512, 91029714, 91629302]
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MicroRNA (miRNA) dysregulation has been associated with carcinogenesis in many cancers, including human colorectal cancer (hCRC). However, the effect and mechanism of miR-377-3p on CRC remains elusive. Herein, we first found that miR-377-3p was upregulated in CRC tissues and promoted tumorigenic activity by accelerating the G(1)-S phase transition, promoting cell proliferation and epithelial-mesenchymal transition (EMT) while repressing apoptosis in CRC cells. Glycogen synthase kinase-3 (GSK-3) was a direct target of miR-377-3p, and upregulated by miR-377-3p. Knockdown of GSK-3 partly rescued miR-377-3p-mediated malignancy characteristics. Most importantly, we showed that miR-377-3p promoted carcinogenesis by activating NF-B pathway. Taken together, our results first reported that miR-377-3p functions as an oncogene and promotes carcinogenesis via upregulating GSK-3 expression and activating NF-B pathway in hCRC cells.
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