title: HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer.
abstract: We previously reported the frequent overexpression of HOX Antisense Intergenic RNA (HOTAIR) in human cervical cancer, which was significantly correlated with tumor progression and poor prognosis. In the present study, we investigated the detailed biological functions of HOTAIR in cervical cancer. In vitro, upregulation of HOTAIR inhibited apoptosis and promoted cellular proliferation, cell cycle progression, migration, and invasion; on the contrast, downregulation of HOTAIR induced more apoptosis, suppressed cellular proliferation, cell cycle, migration, and invasion. Moreover, a high level of HOTAIR was notably associated with radio-resistance and downregulation of p21 in the primary cultured cervical cancer cells. Further, we demonstrated that elevated HOTAIR could induce radio-resistance via inhibiting p21 in HeLa cells, while knockdown of HOTAIR upregulated p21 and consequentially increased the radio-sensitivity of C33A cells. Consistently, stable knockdown of HOTAIR significantly suppressed tumor growth and sensitized cervical cancer to radiotherapy in vivo. In conclusion, HOTAIR served as an onco-lncRNA in cervical cancer which could enhance various aggressive biological behaviors. Moreover, we proved that HOTAIR execute its functions mainly through inhibiting the p21 expression. These results proposed that targeting HOTAIR might be a potent therapeutic strategy in cervical cancer, especially for those patients who accepted radiotherapy.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.forename: Wang
authors.initials: W
authors.lastname: Yuan
authors.forename: Dong
authors.initials: D
authors.lastname: Ruofan
authors.forename: Yu
authors.initials: Y
authors.lastname: Jinjin
authors.forename: Qiu
authors.initials: Q
authors.lastname: Haifeng
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D054462:p21-Activated Kinases / Q000096:biosynthesis*
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D054462:p21-Activated Kinases