The role of miRNA-377 as a tumor suppressor in lung cancer by negative regulation of genes belonging to ErbB signaling pathway

• Published in: Molecular biology reports 2022, Vol.49 (1), p.85-95
• Main Authors: Hashemi, Saba, Yari, Naghmeh, Rahimi Jamnani, Fatemeh, Mahdian, Reza, Karimi, Morteza, Zeinali, Sirous, Rafiee, Mohammad Hesam, Azizi, Masoumeh
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; A549 Cells; Animal Anatomy; Animal Biochemistry; Apoptosis; Biomedical and Life Sciences; Carcinoma, Non-Small-Cell Lung - genetics; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Down-Regulation; Epidermal growth factor receptors; ErbB protein; ErbB Receptors - genetics; Gene Expression Regulation, Neoplastic; Gene regulation; Gene silencing; Histology; Humans; Life Sciences; Lung cancer; Lung Neoplasms - genetics; MicroRNAs - genetics; miRNA; Mitogen-Activated Protein Kinase 1 - genetics; Morphology; mRNA; Non-small cell lung carcinoma; Original Article; p21-Activated Kinases - genetics; Signal Transduction; Therapeutic targets; Transfection; Tumor cell lines; Tumor suppressor genes; Tumors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06844-6

Background The ErbB signaling pathway plays important role in the pathogenesis of lung cancer. We explored the role of miRNA-377 as a tumor suppressor in NSCLC through silencing of some genes in the ErbB pathway. Methods and Results The targeting effect of miRNA-377 on EGFR, MAPK1, ABL2, and PAK2 was evaluated. The expression levels of these genes and miRNA-377 were surveyed in NSCLC and normal human tissues, Calu-6, and A549 cells. Real-time PCR was used to figure out whether miRNA-377 could decrease the target genes mRNAs in transfected lung cancer cell lines. The effects of miRNA-377 on apoptosis cell and proliferation were analyzed. We showed that miRNA-377 targets EGFR, MAPK1, and PAK2 mRNAs in in-silico and luciferase reporter assay. The expression of miRNA-377 was significantly downregulated in human NSCLC tissues, Calu-6 and A549 cells compared to their controls. We observed a negative correlation between EGFR, MAPK1, PAK2, and miRNA-377 expression in human NSCLC tissues. A significant reduction in EGFR, MAPK1, and PAK2 mRNA levels was detected, following miRNA-377 transfection in Calu-6 and A549 cells. The higher levels of miRNA-377 in Calu-6, and A549 cells induced apoptosis and reduced proliferation, significantly. Conclusions All these data reveal that miRNA-377 functions as a tumor suppressor in NSCLC and may serve as a potential therapeutic target for the treatment of NSCLC.