MiR-335-5p restores cisplatin sensitivity in ovarian cancer cells through targeting BCL2L2.
MiR-335-5p restores cisplatin sensitivity in ovarian cancer cells through targeting BCL2L2.
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作者：
Liu R;Guo H;Lu S
我们的研究旨在探索 miR-335-5p 和 BCL2L2 的关联，并研究 miR-335-5p/BCL2L2 轴对顺铂耐药卵巢癌细胞的影响。微阵列分析用于确定原代细胞和顺铂耐药 A2780 细胞中差异表达的 microRNA。通过细胞功能实验探讨miR-335-5p对A2780细胞顺铂敏感性的影响。通过荧光素酶测定验证了 BCL2L2 mRNA 和 miR-335-5p 之间的靶向关系。进行肿瘤异种移植以确认 miR-335-5p 在恢复卵巢癌细胞顺铂敏感性中的功能。 MiR-335-5p 在顺铂耐药的 A2780 细胞中低表达。 miR-335-5p 的过度表达会降低细胞存活率并增强顺铂诱导的细胞凋亡。 BCL2L2 mRNA 是 miR-335-5p 的靶标，沉默 BCL2L2 对细胞活力的影响与 miR-335-5p 过表达相似。 miR-335-5p表达上调通过抑制BCL2L2增强卵巢癌细胞的顺铂敏感性，表明miR-335-5p/BCL2L2轴有可能作为卵巢癌患者顺铂耐药的治疗靶点。
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. 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. 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. 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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