Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21

Kexing Lyu; Yang Xu; Huijun Yue; Yun Li; Jing Zhao; Lin Chen; Jianhui Wu; Xiaolin Zhu; Liping Chai; Chunwei Li; Weiping Wen; Wenbin Lei

doi:10.2147/CMAR.S213690

Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21

Cancer Manag Res. 2019 Sep 17:11:8487-8498. doi: 10.2147/CMAR.S213690. eCollection 2019.

Authors

Kexing Lyu^#¹, Yang Xu^#¹, Huijun Yue¹, Yun Li¹, Jing Zhao², Lin Chen¹, Jianhui Wu³, Xiaolin Zhu¹, Liping Chai¹, Chunwei Li¹, Weiping Wen¹, Wenbin Lei¹

Affiliations

¹ Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
² Department of Otolaryngology, The Third Hospital of Heibei Medical University, Shijiazhuang, People's Republic of China.
³ Department of Otolaryngology, Meizhou People's Hospital, Meizhou, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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: GAS5; LSCC; apoptosis; long noncoding RNA; miR-21; proliferation.