Cervical cancer is the fourth most common cause of mortality in women worldwide. In this study we investigated the effect of a tumour suppressor microRNA miR-214 in modulating the cell death against chemotherapeutic drugs like Doxorubicin, Cisplatin and Paclitaxel. CRISPR-facilitated knockdown and plasmid-based overexpression of miR-214 was performed in cervical cancer cell lines HeLa, C33A and CaSki. It was observed that knocking out miR-214 resulted in reduced apoptosis and cell migration upon drug treatments; while overexpression of miR-214 resulted in marginal increase in apoptosis and cell migration when treated with drugs. However, miR-214 had very little effect on production of reactive oxygen species. Our results also indicate that Doxorubicin was least effective and Paclitaxel most effective in inducing cell death. A combination of miR-214 overexpression and Paclitaxel treatment was found to be most effective in inducing cell death in cervical cancer cells. Analysis of cell cycle phases followed by apoptotic markers also showed that miR-214 overexpression along with Paclitaxel treatment caused an increase in PARP and decline of PI-3 kinase/Akt levels. Therefore, miR-214 levels determine the fate of the cancer cell during chemotherapeutic treatment.

中文翻译：

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CRISPR 介导的 miR-214 敲低调节细胞命运以响应 HPV 阴性和 HPV 阳性宫颈癌细胞中的抗癌药物

宫颈癌是全球女性死亡的第四大常见原因。在这项研究中，我们研究了肿瘤抑制因子 microRNA miR-214 在调节细胞死亡对化疗药物（如阿霉素、顺铂和紫杉醇）的影响。在宫颈癌细胞系 HeLa、C33A 和 CaSki 中进行了 CRISPR 促进的敲低和基于质粒的 miR-214 过表达。据观察，敲除 miR-214 导致药物治疗后细胞凋亡和细胞迁移减少；而当用药物治疗时，miR-214的过表达导致细胞凋亡和细胞迁移的边缘增加。然而，miR-214 对活性氧的产生影响很小。我们的结果还表明，在诱导细胞死亡方面，阿霉素最不有效，而紫杉醇最有效。发现 miR-214 过表达和紫杉醇治疗的组合在诱导宫颈癌细胞死亡方面最有效。随后对细胞周期阶段进行的细胞凋亡标记分析还表明，miR-214 过表达和紫杉醇处理导致 PARP 增加和 PI-3 激酶/Akt 水平下降。因此，miR-214 水平决定了化疗期间癌细胞的命运。