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Hsa-miR-3658 down-regulates OCT4 gene expression followed by suppressing SW480 cell proliferation and migration.

Biochem J. 2020 Jun 26;477(12):2281-2293
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摘要


The pluripotency factor, OCT4 gene is a stemness marker that is involved in the tumorigenicity of different cancer types and knowing about molecular mechanisms of its regulation is crucially important. To date, a few microRNAs (miRNAs) are known to be regulators of OCT4 gene expression. Looking for the novel miRNAs which are capable of regulating OCT4 gene expression, our bioinformatics analysis introduced hsa-miR-3658 (miR-3658) as a bona fide candidate. Then, RT-qPCR results indicated that miR-3658 expression is decreased in colorectal cancer (CRC) tumor tissues, compared with normal pairs. Furthermore, RT-qPCR and western blot analysis showed that the OCT4 gene has been down-regulated following the miR-3658 overexpression. Consistently, dual-luciferase assay supported the direct interaction of miR-3658 with the 3'-UTR sequence of OCT4 gene. Unlike in HCT116 cells, overexpression of miR-3658 in SW480 cells brought about growth inhibition, cell cycle arrest and reduced cell migration, detected by flow cytometry, and scratch test assay. Overall, these findings demonstrated that miR-3658 as a tumor suppressor miRNA exerts its effect against OCT4 gene expression, and it has the potential of being used as a prognostic marker and therapeutic target against colorectal cancer.

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