Inhibition of miR‐578 through SOCS2‐dependent manner reverses gefitinib resistance in NSCLC cells

Abstract

AbstractBackgroundNonsmall‐cell lung cancer (NSCLC) has emerged as one of the dreadful lung cancers globally due to its increased mortality rates. Concerning chemotherapy, gefitinib has been employed as an effective first‐line treatment drug for NSCLC. Nonetheless, the acquired resistance to gefitinib has remained one of the treatment obstacles of NSCLC, requiring improvement in the therapeutic effect of gefitinib.MethodsInitially, reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR), and Western blotting (WB) analyses were conducted to measure micro‐ribose nucleic acid (miRNA, specifically miR‐578) and suppressor of cytokine signaling 2 (SOCS2) levels in the clinical samples. Further, NSCLC cell lines resistance to gefitinib, established in vitro, were transfected by miR‐578 inhibitor, miR‐578 mimic, and si‐SOCS2. Similarly, the xenograft mouse model in vivo was constructed to validate the reversing effect of miR‐578.ResultsOur findings indicated the increased miR‐578 expression levels in the gefitinib resistance group. Further, inhibiting the miR‐578 expression substantially reversed the gefitinib resistance. In addition, the miR‐578 effect was modulated via the SOCS2 expression level. The decreased gefitinib resistance effect of miR‐578 was weakened by inhibiting the SOCS2 expression.ConclusionThese findings demonstrated that miR‐578 effectively abolished gefitinib resistance by regulating the SOCS2 expression within NSCLC cells in vitro and in vivo. Together, these results will undoubtedly support a reference to provide potential molecular therapeutic targets and clinical treatments for treating NSCLC patients.