The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2

C.-H. Xu, L.-M. Xiao, Y. Liu, L.-K. Chen, S.-Y. Zheng, E.-M. Zeng, D.-H. Li

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China. lidonghaildh@outlook.com

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• Oncology

OBJECTIVE: Long noncoding RNAs (lncRNAs) serve as important regulators of diverse types of cancer, including glioma. Nevertheless, their precise roles in cancers remain sufficiently unexplored.

PATIENTS AND METHODS: Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to determine the levels of HOMEOBOX A11 antisense RNA (HOXA11-AS) and miR-130a-5p in glioma tissues and cell lines. Short hairpin RNAs (shRNAs) targeting HOXA11-AS or pcDNA3.1 were transfected into cells via a vector encoding HOXA11-AS to decrease or increase the level of HOXA11-AS. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, flow cytometry and transwell assays were applied to assess the role of HOXA11-AS in glioblastoma cell growth, apoptosis and aggressiveness. The expression of N-cadherin and E-cadherin was determined using immunofluorescence staining. The expression of high-mobility group protein B2 (HMGB2) was determined using Western blot analysis in vitro and immunohistochemistry (IHC) staining in vivo. The direct target of HOXA11-AS and miR-130a-5p was confirmed using the Luciferase reporter assay. Glioblastoma cells were subcutaneously implanted into nude mice to determine the role of HOXA11-AS in tumor growth in vivo.

RESULTS: In the current study, we demonstrated that the lncRNA HOXA11-AS was overexpressed in glioma. The overexpression of HOXA11-AS was correlated with advanced stages of glioma and poor prognosis. Downregulating HOXA11-AS expression significantly suppressed the proliferation, migration and invasion of glioma cells and increased their apoptosis. The growth of glioma cells in vitro was also suppressed by the downregulation of HOXA11-AS. Finally, we revealed that HOXA11-AS exerted its oncogenic effects by binding to miR-130a-5p, thereby neutralizing the suppressive effect of miR-130a-5p on HMGB2.

CONCLUSIONS: Our results demonstrate that HOXA11-AS regulates the growth and metastasis of glioma by targeting the miR-130a-5p-HMGB2 signaling axis.

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