4.7 Article

miRNA-495 suppresses proliferation and migration of colorectal cancer cells by targeting FAM83D

期刊

BIOMEDICINE & PHARMACOTHERAPY
卷 96, 期 -, 页码 974-981

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.11.138

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miR-495; Colorectal cancer; FAM83D; Proliferation; Tumor suppressor

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microRNAs (miRNAs) have been reported to play crucial roles in malignant tumor progression, including cell development, proliferation, and progression. Increasing evidence suggests that miR-495 functions as either an oncogene or tumor suppressor in several tumor types. However, its biological role in the development of colorectal cancer (CRC) still remains unclear. In this study, we found that miR-495 expression level was remarkably down-regulated in CRC tissues samples and cell lines when compared to adjacent normal tissues and cell line by using qRT-PCR detection. Ectopic expression of miR-495 by mimic transfection significantly suppressed CRC cell proliferation and colony formation, inhibited migration and invasion, and induced apoptosis according to CCK-8, colony formation, transwell, and flow cytometry assays. Furthermore, bioinformatics and luciferase reporter assays verified that family with sequence similarity 83, member D (FAM83D) was a direct target of miR-495 in CRC cells, and FAM83D was confirmed to be upregulated in human CRC tissues and reversely correlated with miR-495 expression. In addition, rescue experiments revealed that restoration of FAM84D could partially abrogate the inhibitory effect of miR-495 overexpression on CRC cell proliferation and metastasis. Further mechanic investigations also verified that the PTEN/P13K/AKT/mTOR pathway was involved in the miR-495/FAM83D-mediated CRC cell progression. Our findings identified that miR-495 acted as a critical tumor suppressor by directly targeting FAM83D during CRC development and therefore represented as a potential bio-marker for CRC therapy.

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