Cancer Management and Research (Sep 2019)
Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21
Abstract
Kexing Lyu,1,* Yang Xu,1,* Huijun Yue,1 Yun Li,1 Jing Zhao,2 Lin Chen,1 Jianhui Wu,3 Xiaolin Zhu,1 Liping Chai,1 Chunwei Li,1 Weiping Wen,1 Wenbin Lei1 1Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Otolaryngology, The Third Hospital of Heibei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Otolaryngology, Meizhou People’s Hospital, Meizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiping Wen; Wenbin LeiDepartment of Otolaryngology, The First Affiliated Hospital of Sun Yet-Sen University, Yuexiu, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20 8733 3733Fax +86 20 8733 3108Email [email protected]; [email protected]: Long noncoding RNAs (lncRNAs) have been identified as an important class of noncoding RNAs that are deeply involved in multiple biological processes in tumorigenesis. This study is to investigate the critical roles and biological function of lncRNA growth arrest-specific 5 (GAS5) in tumorigenesis of laryngeal squamous cell carcinoma (LSCC).Patients and methods: A total of 59 samples of LSCC and paired adjacent tissue, as well as corresponding clinicopathological information were collected. GAS5 expression in both LSCC tissues and human SUN1076 and SNU899 cell lines were analyzed by Real-time quantitative RT-PCR method. Ectopic expression of GAS5 by vector transfection in LSCC cell lines and followed by in vitro experiments was to investigate the critical roles and function of GAS5 in LSCC. Cell Counting Kit 8 (CCK8) assay and PE/7AAD Annexin V Apoptosis analysis was to evaluate cell proliferation ability and cell apoptosis. Co-transfection of GAS5 and miR-21 was to explore the interaction between GAS5 and miR-21 in LSCC. BAX and CDK6 protein level were analyzed by western blot method.Results: This study demonstrated that GAS5 was significantly downregulated in LSCC tissue and human LSCC cell lines. GAS5 levels were correlated with the clinicopathological features of LSCC patients. In addition, the ectopic expression of GAS5 significantly inhibited cell proliferation and promoted apoptosis. Co-expression analyses indicated that GAS5 is negatively correlated with miR-21 in LSCC tissues. Overexpression of miR-21 eliminated GAS5-mediated cell apoptosis and proliferation suppression. Furthermore, GAS5, which upregulated BAX mRNA expression and downregulated CDK6 mRNA expression, was reversed by ectopic expression of miR-21.Conclusion: GAS5 suppresses LSCC progression through the negative regulation of miR-21 and its targets involved in cell proliferation and apoptosis, indicating that GAS5 may serve as a biomarker and potential target for LSCC therapy.Keywords: long noncoding RNA, GAS5, LSCC, miR-21, proliferation, apoptosis
