title: miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1.
abstract: Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3'-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity.
authors.affiliation: Cangzhou Central Hospital, Hebei 061001, China.
authors.forename: Shikai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Cangzhou Central Hospital, Hebei 061001, China. Electronic address: commasll@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.affiliation: Cangzhou Central Hospital, Hebei 061001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cangzhou Central Hospital, Hebei 061001, China.
authors.forename: Saitian
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Cangzhou Central Hospital, Hebei 061001, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Gao
mesh_terms: D052685:Alphapapillomavirus / Q000472:pathogenicity*; D001483:Base Sequence; D002453:Cell Cycle; D017931:DNA Primers; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011836:Radiation Tolerance; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology
chemical_list: D017931:DNA Primers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
keywords: Cervical cancer; HR-HPV; Radioresistance; miR-21