The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression
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Cancer Cell International Open Access
PRIMARY RESEARCH
The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression Jian Liu1,2 , Kai Li2†, Rui Wang2†, Sisi Chen2, Jie Wu2, Xiang Li2, Qian Ning1, Ganghua Yang3* and Yamei Pang1*
Abstract Background: Activating transcription factor 2 (ATF2), a member of the activator protein 1 (AP-1) transcription factor family, has been shown to be involved in the pathobiology of numerous cancers. However, the biological role and mechanism of ATF2 in lung adenocarcinoma (LUAD) remains to be elucidated. Methods: The expression of ATF2, NEAT1 and miR-26a-5p in LUAD tissues and cell lines was detected by qRT-PCR and western blotting. The interaction between ATF2, NEAT1, and miR-26a-5p was validated by chromatin immunoprecipitation, luciferase reporter assay and RNA immunoprecipitation. Cell proliferation, invasion and tumorigenesis of LUAD cells were analyzed by using CCK8, transwell invasion assay and xenograft tumor model. Results: We confirmed that ATF2 expression was increased in LUAD tissues compared with normal adjacent lung tissues. Functional experiments showed that ATF2 positively regulated cell proliferation and invasion in LUAD cells. Moreover, we identified that NEAT1 expression was increased in LUAD tissues and positively correlated with ATF2 expression. Mechanistically, ATF2 could bind to the promoter of NEAT1 to promote its transcription. Rescue experiments showed that ATF2 exerted its oncogenic function in LUAD, at least, partly through NEAT1 upregulation. In turn, NEAT1 could positively regulate ATF2 expression and form a positive feedback loop in LUAD cells. Furthermore, we demonstrated that NEAT1 positively regulated ATF2 expression via sponging miR-26a-5p. Conclusion: ATF2 and NEAT1 form a positive feedback loop mediated by miR-26a-5p and coordinately contribute to LUAD progression. Keywords: ATF2, NEAT1, miR-26a-5p, Lung adenocarcinoma Background Lung cancer is one of the most prevalent malignant tumors and the leading cause of cancer related mortality worldwide [1]. Lung adenocarcinoma (LUAD), a major *Correspondence: [email protected]; [email protected] † Jian Liu, Kai Li and Rui Wang contributed equally to this work 1 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xian 710061, Shaanxi, China 3 Department of Geriatric Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xian, Shaanxi 710061, People’s Republic of China Full list of author information is available at the end of the article
histological subtype of lung cancer, accounts for 40% of lung cancer cases and leads to 500,000 cancer related death every year [2]. Although great progress has been made in the diagnosis and treatment in the past years, the average five-year survival rate of LUAD patients remains less than 20% due to tumor heterogeneity and aggressiveness [3]. In order to improve the clinical outcomes of LUAD patients, a deep-going investiga
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