Long-Noncoding RNA CASC9 Promotes Progression of Non-Small Cell Lung Cancer by Promoting the Expression of CDC6 Through Binding to HuR

• Main Authors: Zhang X, Lian T, Fan W, Zhang G, Chen Z, Gou X, Jha RK
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: Cancer Management and Research
• Subjects: lncrna; non-small cell lung cancer; proliferation; migration; cell cycle
• Online Access: https://www.dovepress.com/long-noncoding-rna-casc9-promotes-progression-of-non-small-cell-lung-c-peer-reviewed-article-CMAR

Xudong Zhang,1,* Ting Lian,2,* Wenjun Fan,3 Guangwei Zhang,4 Ziwei Chen,2 Xingchun Gou,5 Rajiv Kumar Jha1 1China-Neal Friendship Medical Research Center of Rajiv Kumar Jha, School of Clinical Medicine, Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, People’s Republic of China; 2Research Center for Prevention and Treatment of Respiratory Disease, School of Clinical Medicine, Xi’an Medical University, Xi’an, People’s Republic of China; 3Department of Neurology, First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 4School of Public Health, Xi’an Medical University, Xi’an, People’s Republic of China; 5Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingchun Gou; Rajiv Kumar Jha Email [e-mail]; [e-mail]: The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular processes in non-small cell lung cancer (NSCLC). However, the understanding of biological functions and detailed mechanisms of lncRNAs is still limited. Herein, the lncRNA cancer susceptibility candidate 9 (CASC9) on NSCLC progression is investigated.Materials and Methods: Expressions of CASC9, HuR and cell division cycle 6 (CDC6) in NSCLC tissues were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The cell counting kit-8, transwell assays, and flow cytometry were used to examine cell proliferation, migration, and the cell cycle. Tumor growth in vivo was evaluated by xenograft tumor experiments and immunohistochemistry. RNA-binding protein immunoprecipitation (RIP) was used to identify the interaction between HuR and CDC6, and CASC9 and HuR.Results: CASC9, CDC6 and HuR expression were found significantly upregulated in NSCLC tissues, which predicted poorer 5-year overall survival in NSCLC patients. Inhibition of CASC9 significantly reduced the malignancy of NSCLC cells, such as proliferation, migration and cell cycle. In vivo experiments further demonstrated that CASC9 knockdown reduced the tumor growth and the Ki-67 expression. Moreover, CASC9 knockdown inhibited the expression of CDC6 which was detected overexpressed in NSCLC tumor tissues. Then, up-regulation of CDC6 could partly reverse the negative effects of CASC9 on cell proliferation, migration and cell cycle. RIP assay and rescue experiment showed that CASC9 regulated CDC via binding to HuR.Conclusion: Our results indicate that CASC9 conferred an aggressive phenotype in NSCLC and might be a pivotal target for this disease.Keywords: lncRNA, non-small cell lung cancer, proliferation, migration, cell cycle