A Long Noncoding RNA HOXA-AS2 Promotes Tumorigenesis And Predicts Poor Prognosis In Ovarian Cancer

[Background]Current evidence suggests that some long noncoding RNAs(lncRNA)play important roles in regulating various biological processes in cancer,including proliferation and apoptosis.However,little is known about the association between HOXA-AS2 expression and proliferation in epithelial ovarian cancer(EOC).In this study,we aimed to further elucidate the role and potential mechanism of HOXA-AS2 in ovarian cancer.[Methods]The level of HOXA-AS2 was detected in 73 EOC tissues and normal tissues by qRT-PCR.SiRNA targeting human HOXA-AS2 and one negative control siRNAwere transfected into ovarian cancer cell lines.Cell proliferation and apoptosis assay were conducted.Besides,tumor formation and IHC assay were done to evaluate the function in vivo.Finally,western blot assay was designed to explore the possible mechanism of HOXA-AS2.[Results]Results showed that not only HOXA-AS2 was aberrantly upregulated in EOC tissues,but also correlated with status of tumor size and FIGO stage.Further,the overall survival in EOC patients with high expression of HOXA-AS2 was inferior to that with low expression.Knockdown of HOXA-AS2 expression significantly inhibited cell proliferation by promoting apoptosis both in HO-8910 and SKOV3 cells.In vivo experiment also revealed that knockdown HOXA-AS2 inhibited HO-8910 cells proliferation.Finally,Western blot results showed that expression of procaspase-9,-8,-3,and PARP(116KDa)decreased after knockdown HOXA-AS2,while cleaved Caspase-9,-8 and-3 increased.At the same time,the expression of Bcl-2 and Bid decreased and Bax increased.Besides,the IHC assay showed that the expression of Bcl-2 and Bid decreased and Bax increased.In conclusion,our study suggests that IncRNA HOXA-AS2 acts as a functional oncogene for EOC partly suppressing the intrinsic mitochondria pathway and extrinsic death receptor pathway,which are associated with Bcl-2 protein family;HOXA-AS2 may be a new prognostic biomarker for EOC and potential target for therapy.[Conclusion]HOXA-AS2 acts as an oncogene in ovarian cancer and promotes proliferation and inhibits apoptosis in vivo and in vitro.