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MiR-335-5p restores cisplatin sensitivity in ovarian cancer cells through targeting BCL2L2.

Cancer Med. 2018 Sep;7(9):4598-4609. doi:10.1002/cam4.1682. Epub 2018 Jul 17
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摘要


OBJECTIVE:Our study was designed to explore the association miR-335-5p and BCL2L2 and to investigate the influence of miR-335-5p/BCL2L2 axis on cisplatin-resistant ovarian cancer cells. METHODS:Microarray analysis was used to determine differentially expressed microRNAs in primary and cisplatin-resistant A2780 cells. Cell function experiments were conducted to investigate the effect of miR-335-5p on the cisplatin sensitivity of A2780 cells. The targeted relationship between BCL2L2 mRNA and miR-335-5p was validated through luciferase assay. Tumor xenograft was performed to confirm the function of miR-335-5p in restoring the cisplatin sensitivity of the ovarian cancer cells. RESULTS:MiR-335-5p was lowly expressed in cisplatin-resistant A2780 cells. Overexpression of miR-335-5p reduced cell survival and enhanced cisplatin-induced cell apoptosis. BCL2L2 mRNA was a target of miR-335-5p, and silencing of BCL2L2 showed the similar results on the cell viability as miR-335-5p overexpression. CONCLUSION:Upregulation of miR-335-5p expression enhanced the cisplatin sensitivity of ovarian cancer cells through suppressing BCL2L2, suggesting the potential of miR-335-5p/BCL2L2 axis as a therapeutic target for the cisplatin resistance of patients with ovarian cancer.

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