MicroRNA-200a Targets EGFR and c-Met to Inhibit Migration, Invasion, and Gefitinib Resistance in Non-Small Cell Lung Cancer

Abstract

Lung cancer, especially non-small cell lung cancer (NSCLC), is the major cause of cancer death worldwide. Mutations in epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met), both of which are receptor tyrosine kinases, have been identified in a considerable percentage of NSCLC patients. EGFR and c-Met share the same downstream pathways and cooperate not only in promoting metastasis but also in conferring resistance to tyrosine kinase inhibitor (TKI) therapies in NSCLC. MicroRNAs (miRNAs) are a family of small non-coding RNAs, usually 21-25 nucleotides long, and are critical in regulating gene expression. Abnormal miRNA expression has been implicated in the initiation and progression in many forms of cancers, including lung cancer. In this study, we found that miR-200a is downregulated in NSCLC cells, where it directly targets the 3′-UTR of both EGFR and c-Met mRNA. Overexpression of miR-200a in NSCLC cells significantly downregulates both EGFR and c-Met levels and severely inhibits cell migration and invasion. Moreover, in NSCLC cell lines that are resistant to gefitinib, a drug often used in TKI therapies to treat NSCLC, miR-200a expression is able to render the cells much more sensitive to the drug treatment.

Identification of differentially expressed miRNAs through high-throughput sequencing in the chicken lung in response to Mycoplasma gallisepticum HS

“…Members of the miR-499 family, such as miR-449, may affect cell proliferation, cell differentiation, cell apoptosis and the cell cycle by regulating target genes directly or indirectly and are closely correlated with the occurrence and development of gastric cancer (Lizé et al, 2011). miRNAs of the miR-8 family can affect host innate defenses against microbial pathogens (Wendlandt et al, 2012;Zhen et al, 2015). The miR-17 family is implicated in the modulation of NF-κB-driven inflammation (Gantier et al, 2012).…”

MiRNA-200a expression is inverse correlation with hepatocyte growth factor expression in stromal fibroblasts and its high expression predicts a good prognosis in patients with non-small cell lung cancer

“…However, no significant association was found to be miRNA-200a expression level in cancer cells with respect to OS in patients with NSCLC. There had strong evidence in basic research to demonstrate that miRNA-200a inhibits EMT and suppresses lung cancer cell migration and invasion [16, 23]. Conversely, one function overexpression study has yielded conflicting results on the role of miRNA-200a in lung cancer cell migration [24].…”

miR-137 inhibits the proliferation of human non-small cell lung cancer cells by targeting SRC3

“…There has been a focus on identifying various tumor suppressor genes and oncogenes regulated by miRNAs in lung cancer, which can effect cancer cell survival and proliferation, such as solute carrier family 22 member 18 (SLC22A18) (15), KIT proto-oncogene receptor tyrosine kinase (16), kruppel like factor 8 (17), epidermal growth factor receptor and MET proto-oncogene receptor tyrosine kinase (18). Novel oncogenes and tumor suppressor genes are continuously being identified.…”