miRNA 5100 Exacerbated Cisplatin Chemoresistance in Lung Cancer via Suppressing C/EBP Homologous Protein (CHOP) Expression

Abstract

This study intends to assess CHOP abundance in lung cancer tissues and drug-resistant cell lines, and the mechanisms of miRNA 5100 on lung cancer drug-resistance chemoresistance. Tumor tissues were collected to detect CHOP levels by immunohistochemical staining and PCR. IC50 of cisplatin and other drugs was detected by MTT assay in A549 or A549/CDDP cells. miR-5100 was overexpressed or knocked down by miR-5100 mimics or inhibitor followed by analysis of CHOP and related proteins abundances by Western blot. A549 cells were injected into mice to establish a xenograft model which was treated with cisplatin followed by detecting tumor growth. CHOP abundance presented substantial level in non-cancerous lung tissues, while miR-5100 level was significantly reduced with negative correlation with CHOP in cancer samples. Low CHOP expression was associated with increased tumor grade and death. IC50 of all tested drugs particularly cisplatin was increased in A549/CDDP or H446/CDDP cells, accompanied by reduced CHOP, LC3-II, DR5 and TRB3 mRNA and protein levels. miR-5100 mimics or miR-5100 inhibitor reduced or elevated CHOP level, accompanied by significantly reduced or elevated LC3-II, DR5, TRB3 level and sensitivity to cisplatin respectively. In addition, miR-5100 overexpression did not affect tumor formation but blemished therapeutic effects of cisplatin and reduced CHOP abundance in vivo. miR-5100 could suppress CHOP expression and regulate drug resistance related genes, ultimately exacerbating chemotherapeutic resistance in lung cancer cells.