Research Papers:
Long non-coding RNA HOXA-AS2 promotes tumorigenesis and predicts poor prognosis in ovarian cancer
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Abstract
Changsheng Yan1,2,*, Mi Gong1,*, Yi Jiang1,*, Huijian Li1,3,4,5, Yicong Wan1, Lin Zhang6, Shulin Zhou1 and Wenjun Cheng1
1Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
2Institute for Microbiota Ecology, Medical College of Xiamen University, Xiamen 361000, China
3State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China
4Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
5Wuxi Maternal and Child Health Hospital, Nanjing Medical University, Wuxi 214002, China
6Department of Obstetrics and Gynecology, Zhongda Hospital Affiliated to Southeast University, Medical School, Southeast University, Nanjing 210029, China
*These authors have contributed equally to this work
Correspondence to:
Wenjun Cheng, email: [email protected]
Keywords: epithelial ovarian cancer (EOC); IncRNA-HOXA-AS2; apoptosis; caspase activation; Bcl-2 protein family
Received: June 14, 2017 Accepted: January 02, 2018 Published: January 02, 2018
ABSTRACT
Recent reports confirms that there are some long non-coding RNAs involved in the different biological regulatories in cancer, including proliferation and apoptosis. However, the correlation between the HOXA-AS2 expression and proliferation in epithelial ovarian cancer was not completely investigated. In vivo expression of HOXA-AS2 in 73 epithelial ovarian cancer tissues and 57 normal tissues was determined by qRT-PCR. Results showed that not only HOXA-AS2 was overexpressed in epithelial ovarian cancer tissues, but also had a relationship with the tumor size and FIGO stage of patients. Further, the overall survival in epithelial ovarian cancer patients presenting high expression of HOXA-AS2 was lower to those presenting low expression. Next, the functional effect of HOXA-AS2 was explored via GSEA analysis in ovarian cancer datasets. The results confirmed that HOXA-AS2 was enriched in cell apoptosis and JAK-STAT pathway. Then, EOC cell lines were transfected with HOXA-AS2 siRNA. Cell proliferation was significantly inhibited after knockdown of HOXA-AS2 via promoting apoptosis both in HO-8910 and SKOV3 cells. Reversely, overexpression of HOXA-AS2 in normal ovarian cell line could promote proliferation and inhibit apoptosis. Animal study consistently indicated that lower expression of HOXA-AS2 inhibited proliferation of HO-8910 cells. Finally, Western blot results showed that expressions of procaspase-9, -8, -3, and PARP were decreased after knockdown of HOXA-AS2, while cleaved Caspase-9, -8 and -3 were increased. Meanwhile, expressions of Bcl-2 and Bid were decreased and Bax was increased. In addition, overexpression of HOXA-AS2 increased the level of Bcl-2, Bid, JAK2 and Stat3 while Bax was decreased in HO8910 and SKOV3. Besides, the IHC assay also showed the same expression changes of Bcl-2 and Bax. To sum up, this study suggested that lncRNA HOXA-AS2 acted as an oncogene in EOC that partly inhibited the intrinsic mitochondria pathway and extrinsic death receptor pathway, which was associated with Bcl-2 protein family; HOXA-AS2 would be regarded as a new biological prognosis and potential therapeutic target of epithelial ovarian cancer.
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