Cancer Management and Research (Jul 2021)
LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma
Abstract
Rui Chen,1 Xi Wang,2,3 Shixian Zhou,2,4 Zongyue Zeng2 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Pathology, Central Hospital of Jiangjin District, Chongqing, 402260, People’s Republic of ChinaCorrespondence: Zongyue ZengDepartment of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 23-8895-5532Email [email protected]: Growing evidence suggests that long non-coding RNAs (lncRNAs), such as lncRNA HOXA-AS2, are critical regulators involved in human cancer. However, the biological functions and detailed mechanisms underlying how lncRNA HOXA-AS2 affects oral squamous cell carcinoma (OSCC) remain unexplored.Methods: The expression of lncRNA HOXA-AS2 and miR-567 was determined in OSCC cell lines and clinical tissues by quantitative real-time PCR (qRT-PCR). Target site prediction and luciferase report assays were used to explore their potential interaction and binding sites between lncRNA HOXA-AS2 and miR-567. Overexpression or silencing expression of lncRNA HOXA-AS2 was performed to confirm that miR-567 was suppressed by lncRNA HOXA-AS2. WST-1 assay, crystal staining assay, and cell cycle analysis were used to assess the cell viability and proliferation ability. The target gene of miR-567 was predicted by Targetscan and validated by luciferase report assay as well as qRT-PCR and Western Blot. Xenograft nude mice model was done to demonstrate that lncRNA HOXA-AS2 promoted cell proliferation via targeting miR-567/CDK8 in vivo.Results: LncRNA HOXA-AS2 was up-regulated in OSCC cells and tissues with the expression of miR-567 decreased. The tissue lncRNA HOXA-AS2 expression was found to positively correlate with the TNM stage and lymph node metastasis of OSCC patients. In terms of the mechanism, we found that lncRNA HOXA-AS2 negatively regulates miR-567 expression via a direct interaction. Functionally, overexpression of lncRNA HOXA-AS2 significantly promoted OSCC cell proliferation, while knockdown of lncRNA HOXA-AS2 significantly inhibited it. We also observed that miR-567 directly targets the 3ʹ UTR of CDK8. Moreover, silencing lncRNA HOXA-AS2 inhibited tumor growth with the expression of miR-567 increased and CDK8 decreased in vivo.Conclusion: LncRNA HOXA-AS2 was up-regulated in OSCC, and its up-regulation correlated with poor clinical outcomes. The lncRNA also promoted OSCC cell proliferation by directly binding to miR-567, leading to an increase in CDK8 expression. The potential prognostic value of lncRNA HOXA-AS2 should be explored in future studies.Keywords: LncRNA HOXA-AS2, MiR-567, CDK8, Oral squamous cell carcinoma, Tumor progression
