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    Cisplatin (DDP)‑based chemotherapy is a standard treatment for cervical cancer, although chemotherapy resistance remains a major concern. Hypoxia‑inducible factor‑2 α (HIF‑2α) plays an important role in chemotherapy resistance. MicroRNAs (miRs) can inhibit gene expression by binding to the 3'‑untranslated region of the target gene. The authors' previous study showed that miR‑519d‑3p plays an important role in the regulation of HIF‑2α expression under hypoxic conditions in cervical cancer. However, the function and regulatory mechanisms of the miR‑519d‑3p/HIF‑2α axis in DDP‑resistance in cervical cancer are not fully understood. Therefore, the aim of the present study was to investigate whether the miR‑519d‑3p/HIF‑2α axis increased DDP resistance by regulating the PI3K/AKT signaling pathway. It was found that the expression of miR‑519d‑3p was lower in DDP‑resistant cervical cancer cells (CaSki/DDP and HeLa/DDP) compared with CaSki and HeLa cells under hypoxic conditions. Additionally, miR‑519d‑3p overexpression decreased the IC50 value in CaSki/DDP and HeLa/DDP cells, and inhibited HIF‑2α protein expression and the PI3K/AKT signaling pathway under hypoxic conditions. Furthermore, it was demonstrated that HIF‑2α overexpression reduced the effect of miR‑519d‑3p overexpression on HeLa/DDP and CaSki/DDP cells. Moreover, the present results suggested that HIF‑2α overexpression increased the IC50 value in CaSki/DDP and HeLa/DDP cells. It was also found that HIF‑2α overexpression reduced the effect of miR‑519d‑3p overexpression on the PI3K/AKT signaling pathway. Therefore, the present results indicated that the miR‑519d‑3p/HIF‑2α axis increased DDP resistance of cervical cancer cells by suppressing the PI3K/AKT signaling pathway under hypoxic conditions.

    Citation

    Lixia Jiang, Shaohua Shi, Feng Li, Qiaofa Shi, Tianyu Zhong, Huijuan Zhang, Yu Xia. miR‑519d‑3p/HIF‑2α axis increases the chemosensitivity of human cervical cancer cells to cisplatin via inactivation of PI3K/AKT signaling. Molecular medicine reports. 2021 May;23(5)


    PMID: 33760204

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