MicroRNAs as the critical regulators of tyrosine kinase inhibitors resistance in lung tumor cells

Abstract

Lung cancer is the second most common and the leading cause of cancer related deaths globally. Tyrosine Kinase Inhibitors (TKIs) are among the common therapeutic strategies in lung cancer patients, however the treatment process fails in a wide range of patients due to TKIs resistance. Given that the use of anti-cancer drugs can always have side effects on normal tissues, predicting the TKI responses can provide an efficient therapeutic strategy. Therefore, it is required to clarify the molecular mechanisms of TKIs resistance in lung cancer patients. MicroRNAs (miRNAs) are involved in regulation of various pathophysiological cellular processes. In the present review, we discussed the miRNAs that have been associated with TKIs responses in lung cancer. MiRNAs mainly exert their role on TKIs response through regulation of Tyrosine Kinase Receptors (TKRs) and down-stream signaling pathways. This review paves the way for introducing a panel of miRNAs for the prediction of TKIs responses in lung cancer patients. Video Abstract.

Keywords: Diagnosis; MicroRNA (miRNA); Non-small cell lung cancer (NSCLC); Prognosis; Resistance; Tyrosine kinase inhibitor (TKI).

Fig. 1

Molecular mechanisms of microRNAs involved in regulation of TKIs responses in lung tumor cells. All of the microRNAs that targeted the RTKs were involved in increased TKIs sensitivity in lung tumor cells. MiR-214, miR-21, and miR-23a promoted TKIs resistance through PTEN targeting. SNHG14 and LINC0060 also increased TKIs resistance by miR-206-3p and miR-149-5p targeting and following ABCB1 and IL-6 up regulations in lung tumor cells. MiR-3127-5p and miR-146b-5p were also involved in increased TKIs sensitivity through ABL and IRAK1 targeting, respectively. (Created with BioRender.com)