LRPPRC contributes to the cisplatin resistance of lung cancer cells by regulating MDR1 expression

Abstract

The development of multidrug resistance is the major obstacle to successful lung cancer chemotherapy. Cancer cells gain resistance through increased levels of P-glycoprotein (P-gp), which is encoded by the multidrug resistance-associated protein 1 (MDR1) gene. Leucine-rich PPR motif-containing protein (LRPPRC), a member of the PPR family, has been verified to regulate the transcription of MDR1. This regulation is influenced by the methylation status of the GC -100 box in the MDR1 promoter. The present study aimed to investigate the effect of LRPPRC on cisplatin (DDP) resistance in lung cancer cells and explore the underlying mechanism. DDP-resistant non-small cell lung cancer cell lines (A549/DDP, H1299/DDP) were generated. The expression levels of LRPPRC and P-gp/MDR1, investigated by qPCR and western blot analysis, were increased in the A549/DDP and H1299/DDP cells compared with that in the parental cells. LRPPRC silencing with shRNA increased DDP sensitivity in vitro and in vivo. LRPPRC silencing inhibited the level of LRPPRC binding with the MDR1 promoter, investigated by chromatin immunoprecipitation-qPCR, and the corresponding MDR1 expression. Demethylation treatment rescued the decrease in the level of LRPPRC binding with MDR1 and the corresponding expression of MDR1 and the increase in DDP sensitivity due to LRPPRC silencing. Our study suggests that LRPPRC contributes to DDP resistance in lung cancer cells by regulating MDR1 transcription. Thus, LRPPRC may serve as a potential molecular target for chemo-resistance reversal in lung cancer.

Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death

“…Previous studies have reported that the drug transporter genes MRP1 and MDR1 mediated the development of platinum drug resistance in lung cancer cells [18,19]. Moreover, nucleotide excision repair and base excision repair mechanisms are also said to be able to protect against the cytotoxicity of cisplatin in cancer cells [20].…”

GREM1,LRPPRC and SLC39A4 as Potential Biomarkers of Intervertebral Disc Degeneration:A Bioinformatics Analysis based on Multiple Microarray and Single-cell Sequencing Data

“…The role of this protein is unknown and may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. Various studies demonstrate that high expression of LRPPRC is associated with poor prognosis in a variety of cancers, such as bladder urothelial carcinoma [39], lung cancer [40] and pancreatic cancer [41]. Maimaiti [42] et al de ned LRPPRC as a N6methyladenosine (m6A) modi cation for intracranial aneurysms.…”

LncRNA CTD-3252C9.4 modulates pancreatic cancer cell survival and apoptosis through regulating IFI6 transcription

“…Recent reports indicated that CTD-3252C9.4 is abnormally expressed in multiple cancers. It is found highly expressed in head and neck cancers, hepatocellular carcinoma, colon and ovary cancer [ 13 , 17 ], while significantly reduced in prostate, uterus, breast, and kidney cancers[ 12 ], which indicated that CTD-3252C9.4 has diverse expression patterns in different cancers. The roles of CTD-3252C9.4 in nasopharyngeal and hepatocellular carcinomas have been revealed.…”

“…Increased CTD-3252C9.4 expression was markedly associated with aggressive clinicopathological factors and shorter survival time in patients with hepatocellular carcinoma. Through binding with EZH2 to inhibit E-cadherin expression, CTD-3252C9.4 contributes to hepatocellular carcinoma cell invasion and migration [ 17 ]. The expression and function of CTD-3252C9.4 in pancreatic cancer, however, have not been reported so far.…”