Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/β-catenin pathway in human ovarian cancer.
Overexpression of HOTAIR (HOX antisense intergenic RNA) is significantly correlated with tumor progression and poor prognosis in human ovarian cancer. However, the underlying mechanisms are largely unknown. In the present study, we investigated the roles of HOTAIR in the initiation and chemoresistance of ovarian cancer. As our data show, HOTAIR overexpression promoted cell cycle progression (and thus cell proliferation) by activating the wnt/β-catenin signaling pathway. Likewise, knockdown of HOTAIR suppressed cell proliferation and arrested cell cycle at G1 phase via inhibition of wnt/β-catenin signaling. Moreover, the results of primary culture demonstrated that elevated HOTAIR expression correlated positively with chemoresistance in ovarian cancer. In vitro and in vivo, HOTAIR induced cellular resistance to cisplatin by activating the wnt/β-catenin pathway, which could be reversed by pre-treatment with the wnt/β-catenin inhibitor, XAV939. In conclusion, HOTAIR promotes the initiation and chemoresistance of ovarian cancer by activating wnt/β-catenin signaling, suggesting that HOTAIR might be a potent therapeutic target for ovarian cancer treatment.
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jing
J
Li
Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated International Peace Maternity and Child Health Hospital, No. 910, Hengshan Road, Xujiahui District, Shanghai, 200030, China.
Siqin
S
Yang
Department of Gynecologic Oncology, the Affiliated Cancer Hospital of Zhengzhou University and Henan Provincal Cancer Hospital, Zhengzhou, Henan Province, 450008, China.
Ning
N
Su
Department of Obstetrics and Gynecology, the Affiliated Hospital of Jiangnan University and the 4th People's Hospital of Wuxi, Wuxi, Jiangsu Province, 214062, China.
Yuan
Y
Wang
Department of Obstetrics and Gynecology, the Affiliated Hospital of Jiangnan University and the 4th People's Hospital of Wuxi, Wuxi, Jiangsu Province, 214062, China.
Jinjin
J
Yu
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, No. 1, East Jianshe Road, Erqi District, Zhengzhou, Henan Province, 450052, China. haifengqiu120@gmail.com.
Haifeng
H
Qiu
Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated International Peace Maternity and Child Health Hospital, No. 910, Hengshan Road, Xujiahui District, Shanghai, 200030, China. hexiaoying06@gmail.com.
Xiaoying
X
He
D000368:Aged; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics*
C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding
Cell cycle; Chemoresistance; HOTAIR; Long non-coding RNA; Ovarian cancer; Proliferation