The relationship of selected miRNAs to P-glycoprotein, MRP1 and LRP/MVP mediated drug resistance in non-small cell lung cancer

Lung cancer is classified as one of the most serious causes of cancer mortality worldwide. miRNA s are small non-coding, endogenous, single-strand RNA s that regulating protein levels in cells by cleavage of mRNA target or translational repression. Protein transporters P-gp, MRP1 and LRP/MVP are connected to the emergence of multidrug resistance (MDR ) in non-small cell lung cancer (NSCLC) patients. The aim of this study was to determine whether levels of miR-21, miR-126 and miR-205 are associated with the expression of above mentioned proteins. We analysed miR-21, miR-126 and miR-205 in various histological subtypes of NSCLC and correlated their expression with clinico-pathological characteristics progression free survival (PFS) and overall survival (OS) and with expression of P-gp, MRP1 and LRP/MVP. We found no significant relationships between expression of miR-21 and miR-126 and clinico-pathological parameters. However, miR- 205 level was significantly increased in squamous cell lung cancer (p<10–6) compared to other histological subtypes of NSCLC. Additionally, the level of miR-205 inversely correlated with P-gp expression in NSCLC patients (p=0.03). Our results suggest that miR-205 could be used as a diagnostic marker and its downregulation may indicate the emergence of P-gp mediated drug resistance in NSCLC patients.

This work was supported by grants IGA MZCR NT13569, and CZ.1.05/2.1.00/01.0030