title: MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway.
abstract: 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-1α overexpression. MiR-21 overexpression decreases PTEN, increases p-Akt, and subsequently increases HIF-1α expression, while miR-21 inhibition results in increased PTEN, decreased p-Akt, and then decreased HIF-1α. Therefore, we inferred that there is a HIF-1α-miR-21 positive feedback loop through the PTEN/Akt/HIF-1α 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.
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China. commasll@163.com.
authors.forename: Shikai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
authors.forename: Dongkui
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Cangzhou Central Hospital, No.16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
mesh_terms: D001343:Autophagy; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Cervical cancer; HIF-1α; Radiosensitivity; miR-21