Cancer Management and Research (Sep 2020)
LncRNA GATA6-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer via Repressing microRNA-543 to Up-Regulating RKIP
Abstract
Zixuan Gong,1,* Xiaoyu Chen,2,* YueChao Zhang,3,* Cheng Liu,4 Zhibing Wang,5 Xiaoyan Xu,6 Jun Zhu,7 Tongqing Xue4 1Department of Urology, Jiangsu Provincial People’s Hospital, Nanjing, Jiangsu Province, 211166, People’s Republic of China; 2Department of Radiology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian 223001, Jiangsu Province, People’s Republic of China; 3Department of Pharmacy, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 4Department of Interventional Radiology, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 5Department of Radiology, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 6Department of Drug, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 7Department of Interventional Radiology, The Third People’s Hospital of Yancheng, Yancheng 224001, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tongqing Xue; Jun Zhu Tel +86 51785938616; +86 51581606203Email [email protected]; [email protected]: Much evidence unveils the significance of long non-coding RNAs (lncRNAs) in diverse cancers. This study was designed to clarify the function and mechanism of lncRNA GATA6 antisense RNA 1 (GATA6-AS1) in the progression of non-small cell lung cancer (NSCLC).Methods: GATA6-AS1, miR-543 and Raf kinase inhibitor protein (RKIP) mRNA expressions were detected by qRT-PCR. Chi-square test was adopted to analyze the relationship between GATA6-AS1 expression and the clinicopathological parameters of NSCLC patients. NSCLC cells H1299 and H460 cells were used as overexpression or knockdown models, respectively, and cell proliferation and metastasis were determined by CCK-8 and Transwell assays. RKIP, E-cadherin, N-cadherin, STAT3, p-STAT3 expressions in NSCLC cells were detected by Western blot. The targeting relationship between GATA6-AS1 and miR-543 was confirmed by dual-luciferase reporter assay.Results: GATA6-AS1 was significantly lowly expressed in NSCLC tissues and cell lines, and its low expression level was significantly correlated with larger tumor size and positive lymph node metastasis. GATA6-AS1 overexpression inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition of NSCLC cells, while GATA6-AS1 knockdown caused the opposite effects. Mechanistically, it was confirmed that GATA6-AS1 impeded NSCLC cell proliferation and metastasis by adsorbing miR-543 and up-regulating the expression of RKIP.Conclusions: As a tumor suppressor, GATA6-AS1 participates in suppressing the progression of NSCLC by modulating the miR-543/RKIP axis.Keywords: NSCLC, GATA6-AS1, miR-543, RKIP, proliferation, metastasis
