p53/miR‐30a‐5p/ SOX4 feedback loop mediates cellular proliferation, apoptosis, and migration of non‐small‐cell lung cancer

• Published in: Journal of cellular physiology Vol. 234; no. 12; pp. 22884 - 22895
• Main Authors: Quan, Xiaowei, Li, Xuelian, Yin, Zhihua, Ren, Yangwu, Zhou, Baosen
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2019
• Subjects: Apoptosis; BAX protein; Bioinformatics; Cell migration; Cell proliferation; Chromatin; Feedback; Feedback loops; Immunoprecipitation; Lung cancer; microRNA; MicroRNAs; miRNA; miR‐30a‐5p; Non-small cell lung carcinoma; NSCLC; p53; p53 Protein; Proteins; SOX4; Sox4 protein; Therapeutic applications; Tumorigenesis; microRNA; NSCLC; miR-30a-5p; SOX4; p53
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28851

Many microRNAs (miRNAs) play vital roles in the tumorigenesis and development of cancers. In this study, we aimed to identify the differentially expressed miRNAs and their specific mechanisms in non‐small‐cell lung cancer (NSCLC). Based on data from the GSE56036 database, miR‐30a‐5p expression was identified to be downregulated in NSCLC. Further investigations showed that overexpression of miR‐30a‐5p inhibited cell proliferation, migration, and promoted apoptosis in NSCLC. Increase of miR‐30a‐5p level could induce the increase of Bax protein level and decrease of Bcl‐2 protein level. In addition, chromatin immunoprecipitation assays showed that miR‐30a‐5p expression was induced by binding of p53 to the promoter of MIR30A. Bioinformatics prediction indicated that miR‐30a‐5p targets SOX4, and western blot analysis indicated that overexpression of the miRNA decreases the SOX4 protein expression level, which in turn regulated the level of p53. Thus, this study provides evidence for the existence of a p53/miR‐30a‐5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target. This study provides evidence for the existence of a p53/miR‐30a‐5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target.