MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway

被引:90
作者
Song, Lili [1 ]
Liu, Shikai [1 ]
Zhang, Liang [1 ]
Yao, Hairong [1 ]
Gao, Fangyuan [1 ]
Xu, Dongkui [1 ]
Li, Qian [1 ]
机构
[1] Cangzhou Cent Hosp, Dept Obstet & Gynecol, 16 Xinhua West Rd, Cangzhou 061001, Hebei, Peoples R China
关键词
miR-21; Radiosensitivity; Cervical cancer; HIF-1; alpha; CARCINOMA CELLS; HYPOXIA; EXPRESSION; RADIATION; RESISTANCE; RADIORESISTANCE; ANGIOGENESIS; CONTRIBUTES; MICRORNA-21; APOPTOSIS;
D O I
10.1007/s13277-016-5073-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1 alpha overexpression. MiR-21 overexpression decreases PTEN, increases p-Akt, and subsequently increases HIF-1 alpha expression, while miR-21 inhibition results in increased PTEN, decreased p-Akt, and then decreased HIF-1 alpha. Therefore, we inferred that there is a HIF-1 alpha-miR-21 positive feedback loop through the PTEN/Akt/HIF-1 alpha pathway in cervical cancer cells. In addition, we also demonstrated that miR-21 confers decreased autophagy in cervical cancer cells after IR via the Akt-mTOR signaling pathway. Decreased autophagy is one of the potential mechanisms of increased radioresistance in cervical cancer cells. These findings expand our understanding of radioresistance development in cervical cancer.
引用
收藏
页码:12161 / 12168
页数:8
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