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

Abstract

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.Targeting the 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 gure 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 insilico and luciferase reporter assay. The expression of miRNA-377 was signi cantly 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 signi cant 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, signi cantly. 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.

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

“…Hashemi et al found that miR-377 expression was significantly lower in human NSCLC tissues and cell lines in comparison to the non-tumour tissue samples, and they also reported that miR-377 over-expression reduced the cancer cells’ proliferation and enhanced their apoptosis, thus making it a potential therapeutic target [ 94 ].…”

MiRNAs in Lung Cancer: Diagnostic, Prognostic, and Therapeutic Potential

“…Fluctuations in miRNA expression are the dominant consequence of miRNA deregulation in cancer [ 38 ]. The expression of different miRNAs has been found to be altered in various lung cancer types, such as NSCLC [ 39 , 40 ], lung carcinoids [ 41 , 42 , 43 ], lung adenocarcinoma, large cell neuroendocrine carcinoma, and squamous cell carcinoma [ 44 ] ( Table 1 ).…”

Exosomes as Nanocarriers for Theragnostic miRNA Markers in Nonsmall Cell Lung Cancer Therapy

“…The cyclindependent kinase 8 (CDK8) gene was the therapeutic target to obtain such effects as an outcome [131]. Adding to this, miRNA-377 prevented the proliferation and induced apoptosis in A549 and Calu-6 cells by targeting and downregulating the expressions of EGFR, MAPK1, and PAK2 of ErbB signaling pathway [132].…”