MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients

• Published in: Gene 2020-03, Vol.730, p.144316-144316, Article 144316
• Main Authors: Feng, Yu-Yu, Liu, Cong-Hui, Xue, Yang, Chen, Yuan-Yuan, Wang, Yu-Li, Wu, Xiong-Zhi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Adult; Aged; Aged, 80 and over; Aggressiveness; Carrier Proteins - genetics; Carrier Proteins - metabolism; Case-Control Studies; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Databases, Genetic; Disease Progression; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; Gene Expression Regulation, Neoplastic - genetics; Glycoproteins - genetics; Glycoproteins - metabolism; Humans; Kaplan-Meier Estimate; Lung - metabolism; Lung adenocarcinoma; Lung Neoplasms - genetics; Male; Microfibril-associated glycoprotein 4; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-147b; Prognosis
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2019.144316

•miR-147b was increased in LUAD, which was associated with unfavorable outcome.•MFAP4 was a target gene of miR-147b and its down-regulation was linked with poor prognosis in LUAD.•miR-147b affected cell malignant behaviors by regulating MFAP4. Lung adenocarcinoma (LUAD) is widely known as the leading cause of death in patients with lung cancer. Extensive evidence has determined that microRNAs (miRNAs) exert critical effects on various biological processes in tumorigenesis. microRNA-147b (miR-147b) has been reported to serve as an oncogenic molecule in colorectal cancer and hepatocellular carcinoma, however, its prognostic value and biological effect in LUAD remain rare. miR-147b and microfibril-associated glycoprotein 4 (MFAP4) data were collected from The Cancer Genome Atlas (TCGA) database to determine their expression levels in LUAD tissues. Kaplan-Meier method was used to plot the overall survival curves for the prognostic power of miR-147b and MFAP4 identification. Chi-square test was utilized to demonstrate the association between clinical characteristics and miR-147b or MFAP4 in LUAD. Luciferse reporter assay was implemented to identify the correlation between miR-147b and MFAP4. The mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. To explore the effects of miR-147b and its potential mechanism in LUAD, cell counting kit 8 (CCK-8), colony formation and transwell assays were performed in LUAD cells with abnormal expression of miR-147b or/and MFAP4. Our results showed that miR-147b was up-regulated in LUAD tissues and cell lines, which induced poor outcome. Conversely, MFAP4, the putative target gene of miR-147b, was down-regulated in LUAD. The expression of MFAP4 in LUAD cells was negatively regulated by miR-147b. Results of experiments in vitro revealed that miR-147b could promote cell proliferation, colony formation, invasion and migration, while up-regulation of MFAP4 suppressed the impacts of miR-147b on cell malignant aggressiveness in A549 and Calu-3 cells. In conclusion, these findings determined that miR-147b contributed to the progression of LUAD via targeting MFAP4. Thus, understanding the potential mechanism of miR-147b/MFAP4 may improve the treatment of cancers, especially LUAD.