miR-502-3p 通过靶向结合 CBL 抑制卵巢癌增殖并诱导凋亡

目的 探究微小 RNA 502-3p (micro RNA 502-3p, miR-502-3p) 通过靶向结合 Casitas B 细胞淋巴 瘤 (Casitas B-cell lymphoma, CBL) 参与卵巢癌增殖和凋亡的机制。 方法 下载 GSE66957、 GSE119056、 TCGA_ OV 卵巢癌相关数据矩阵, 分析 miR-502-3p、 CBL 与卵巢癌的关系; 构建过表达 miR-502-3p、 CBL 的 SKOV3 和 HO8910 细胞系, 分别采用细胞计数试剂盒 ( cell counting kit 8, CCK-8)、 克隆形成实验、 流 式细胞术检测细胞增殖和凋亡情况; 通过荷瘤裸鼠实验, 观察过表达 CBL 对肿瘤生长的影响; 验证 miR502-3p 与 CBL 的靶向关系。 结果 生物信息学分析显示, 卵巢癌组织中 CBL 水平高于癌旁组织, miR-502- 3p 水平低于癌旁组织, CBL 水平与患者预后、 细胞增殖基因表达有关 (P< 0. 05)。 miR-502-3p 与 CBL 存在 靶向关系, 与 Vector 组比较, CBL 组肿瘤的体积及重量增加 (P< 0. 05); 与 miR-NC 组比较, miR-502-3p 组 SKOV3、 HO8910 细胞中 CBL 蛋白表达、 细胞活力、 克隆数降低, 细胞凋亡率升高 (P< 0. 05), 但 CBL 可逆转上述细胞变化。 结论 miR-502-3p 可通过靶向下调 CBL 抑制卵巢癌细胞的增殖, 并诱导其凋亡。

miR-502-3 p Inhibit Proliferation and Induce Apoptosis in Ovarian Cancer by Targeting CBL

Objective To explore the effects of micro RNA 502-3p (miR-502-3p) on the proliferation and apoptosis of ovarian cancer cells by targeting Casitas B-cell lymphoma ( CBL). Methods The ovarian cancer related datasets GSE66957, GSE119056 and TCGA _ OV were downloaded and the relationship between ovarian cancer and miR-502-3p or CBL was analyzed. The SKOV3 and HO8910 cell lines with overexpressed miR-502-3p or/ and CBL were constructed. The cell proliferation and apoptosis were detected by cell counting kit 8 (CCK-8), clone formation assay and flow cytometry. The effect of CBL overexpression on tumor growth was observed in tumor bearing nude mice. The targeting relationship between miR-502-3p and CBL was verified. Results Bioinformatics analysis showed that the expression level of CBL in ovarian cancer tissues was higher than that in para-cancerous tissues, while the expression level of miR-502-3p was lower in cancer tissues than in para-cancerous tissues (P < 0. 05). The expression level of CBL was related to the prognosis of ovarian cancer and the expression of cell proliferation-related genes (P < 0. 05). There was a targeting relationship between miR-502-3p and CBL. The volume and weight of tumors were significantly increased in the CBL group compared with the vector group (P< 0. 05). The expression level of CBL protein, cell viability and number of clones formed in SKOV3 and HO8910 cell lines were significantly decreased and the apoptosis rate was significantly increased in the miR-502-3p group compared with the miR-NC group (P < 0. 05). However, CBL overexpression could reversethe above changes. Conclusion miR-502-3p can inhibit the proliferation and induce the apoptosis of ovarian cancer cells by down-regulating CBL.