OncoTargets and Therapy (Nov 2019)
Long Non-Coding RNA HOXA-AS2 Enhances The Malignant Biological Behaviors In Glioma By Epigenetically Regulating RND3 Expression
Abstract
Lixin Wu, Xuqiang Zhu, Zhenyu Song, Di Chen, Mengguo Guo, Junxin Liang, Daling Ding, Weiguang Wang, Dongming Yan Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of ChinaCorrespondence: Dongming YanDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, People’s Republic of ChinaTel +86-0371-67966118Email [email protected]: Long non-coding RNAs (LncRNAs) have been demonstrated to play a vital role in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2), a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes, is identified as an oncogene in several malignancies, including glioma. However, the biological functions of HOXA-AS2 and its underlying molecular mechanisms in glioma progression remain to be investigated.Method: The expression of HOXA-AS2 and RND3 mRNA was determined using qRT-PCR analysis. The protein level of RND3 and EZH2 was measured by Western blot analysis. The biological function of HOXA-AS2 or RND3 in glioma was detected by CCK-8 assay, colony formation assays, transwell assay, and flow cytometry. Dual-luciferase reporter, RIP, RNA-protein pull down and ChIP assays were performed to explore the molecular mechanism of HOXA-AS2 in glioma. The effect of HOXA-AS2 in vivo was examined using xenograft tumor assay.Results: HOXA-AS2 expression was increased in glioma tissues and cells. High HOXA-AS2 expression was associated with larger tumor size and advanced pathological stage. Functionally, knockdown of HOXA-AS2 suppressed cell proliferation and invasion, and promoted apoptosis. Mechanically, HOXA-AS2 epigenetically inhibited RND3 transcription by binding to EZH2. Moreover, overexpression of RND3 exerted similar tumor-suppressive effects to the depletion of HOXA-AS2. Furthermore, the anti-cancer effects induced by si-HOXA-AS2 were greatly reversed by silencing of RND3. Finally, knockdown of HOXA-AS2 impaired tumor growth in vivo possibly via increasing RND3 expression.Conclusion: Taken together, HOXA-AS2 recruits EZH2 to the promoter region of RND3 and inhibits its expression, thereby facilitating glioma progression. Our findings provide a prospective therapeutic strategy for glioma intervention.Keywords: glioma, lncRNA, HOXA-AS2, RND3, EZH2
