CHD1L contributes to cisplatin resistance by upregulating the ABCB1–NF-κB axis in human non-small-cell lung cancer

Abstract

Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a recently identified gene associated with malignant tumor progression and patient chemotherapy resistance in human hepatocellular carcinoma (HCC). Previously, we found an association between CHD1L overexpression and poor patient survival in non-small-cell lung cancer (NSCLC). However, little is known about the relationship between CHD1L expression and chemotherapy resistance of NSCLC. By employing immunohistochemistry, we analyzed the expression of CHD1L in NSCLC samples and elucidated the roles and mechanism of CHD1L in NSCLC chemoresistance. We found that the increased expression of CHD1L is positively correlated with a shorter survival time of patients who had received chemotherapy after surgery. We also found that the expression of CHD1L was increased after cisplatin treatment in A549 cells. Conversely, the depletion of CHD1L in cisplatin-resistance cells increased the cell sensitivity to cisplatin, indicating that CHD1L plays a critical role in cisplatin resistance of NSCLC cells. Importantly, we identified the ATP-Binding Cassette Sub-Family B Member (ABCB1) gene as a potential downstream target of CHD1L in NSCLC cells. Knocking down ABCB1 coupled with ectopic expression of CHD1L enhanced the effect of cisplatin on NSCLC cells apoptosis. In addition, overexpressed CHD1L increase the transcription of c-Jun which targeted directly to the promoter of ABCB1. Our data demonstrate that CHD1L could induce cisplatin resistance in NSCLC via c-Jun-ABCB1–NF-κB axis, and may serve as a novel predictive marker and the potential therapeutic target for cisplatin resistance in NSCLC.

Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations

“…Five of these loci are known to be under recent positive selection, harboring genes involved in immune response (NBPF1 37 , HLA 38 ), nutrition (LCT 39 , LDLR 40 ), and mucus production (MUC2 23 ). We also identified 7 other loci, harboring genes related to immune response (MRC1, playing a role in both the innate and adaptive immune systems 41 , and BCAM, encoding the Lutheran antigen system, also associated with low density lipoprotein cholesterol measurement 42 ), mucus production (CAPN8, involved in gastric mucosal defense 43 ), tumor growth (CHD1L, associated with tumor progression and chemotherapy resistance in human hepatocellular carcinoma 44 , and BANP, encoding a tumor suppressor and cell cycle regulator protein 45 ), as well as genetic disorders (HYDIN, causing primary ciliary dyskinesia 46 , and EFTUD2, causing mandibulofacial dysostosis with microcephaly 47 ). We checked that these regions are not extreme in recombination rate or marker density (Supplementary Table 5).…”

Identity-by-descent detection across 487,409 British samples reveals fine-scale population structure, evolutionary history, and trait associations

“…5 of these loci are known to be under recent positive selection, harboring genes involved in immune response ( NBPF1 (33), HLA (34)), nutrition ( LCT (35), LDLR (36)) and mucus production ( MUC2 (22)). We also detected 7 novel loci, harboring genes related to immune response ( MRC1 , playing a role in both the innate and adaptive immune systems (37), and BCAM , encoding the Lutheran antigen system, also associated with low density lipoprotein cholesterol measurement (38)), mucus production ( CAPN8 , involved in gastric mucosal defense (39)), tumor growth ( CHD1L , associated with tumor progression and chemotherapy resistance in human hepatocellular carcinoma (40), and BANP , encoding a tumor suppressor and cell cycle regulator protein (41)), as well as genetic disorders ( HYDIN , causing primary ciliary dyskinesia (42), and EFTUD2 , causing mandibulofacial dysostosis with microcephaly (43)). We checked that these regions are not extreme in recombination rate or marker density (Supplementary Table 5).…”

A bioinformatics investigation into the pharmacological mechanisms of javanica oil emulsion injection in non-small cell lung cancer based on network pharmacology methodologies

“…Yang et al identified ABCB1 as a vital downstream target of the chromosomal helicase/ATPase DNA-binding protein 1-like gene in NSCLC cells. The knockout of ABCB1 and ectopic expression of the chromosomal helicase/ATPase DNA-binding protein 1like gene enhanced the effect of cisplatin on NSCLC cell apoptosis [73]. Regarding LDLR, Yang et al demonstrated that T lymphocytes (LMPs) exert antiangiogenic and proapoptotic effects that lead to inhibition of lung carcinoma by decreasing the vascular endothelial growth factor levels, and the knockdown of LDLR reduces the uptake of LMPs by Lewis lung carcinoma cells and attenuates the inhibitory effects of LMPs on cell growth and vascular endothelial growth factor expression.…”