A putative competing endogenous RNA network in cisplatin‑resistant lung adenocarcinoma cells identifying potentially rewarding research targets

Abstract

Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer and has a poor 5 year survival rate (<10%). Cisplatin is one of the most effective chemotherapeutic treatments for LUAD, even though it is of limited overall utility due to acquired drug resistance. To identify possible genetic targets for the mitigation of cisplatin resistance, gene expression data from cisplatin-resistant cell lines were integrated with patient information. Expression data for cisplatin-resistant and cisplatin-sensitive A549 cell lines were obtained from the Gene Expression Omnibus database, while LUAD patient data was obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs) and long non-coding RNAs (DElncRNAs) were identified between the cisplatin-sensitive and cisplatin-resistant cells. Using the TCGA patient data, 33 DEmRNAs associated with survival were identified. A total of 74 DElncRNAs co-expressed with the survival-associated DEmRNAs, and 11 DEmiRNAs that regulated the survival-associated DEmRNAs, were also identified. A competing endogenous RNA (ceRNA) network was constructed based on the aforementioned results, which included 17 survival-associated DEmRNAs, 9 DEmiRNAs and 16 DElncRNAs. This network revealed 8 ceRNA pathway axes possibly associated with cisplatin resistance in A549 cells. Specifically, the network suggested that the lncRNAs HOXD-AS2, LINC01123 and FIRRE may act as ceRNAs to increase cisplatin resistance in human LUAD cells. Therefore, it was speculated that these lncRNAs represent potentially rewarding research targets.

DNMT3B regulates proliferation of A549 cells through the microRNA‑152‑3p/NCAM1 pathway

“…The present study demonstrated that knockdown of DNMT3B could increase miR-152-3p and, thereby inhibiting cell proliferation. Since DNMT3B can bind to and methylate the core region of miR-152-3p, bioinformatics analysis was performed to investigate the in-depth mechanism of miR-152-3p in the progression of NSCLC, and NCAM1 was identified as a new target gene of miR-152-3p in lung cancer cells ( 17 ). Via RT-qPCR and western blotting experiments it was revealed that miR-152-3p could suppress NCAM1.…”

“…miR-152 belongs to the miR-148/152 family, and it has been indicated to be downregulated in the cytoplasm in NSCLC ( 16 ). Our previous study used bioinformatics analysis and revealed that miR-152-3p was a cisplatin resistance-associated miRNA ( 17 ). The target genes of miR-152-3p were initially predicted using TargetScan and PicTar databases, which uncovered a binding site for miR-152-3p on the mRNA of neural cell adhesion molecule 1 (NCAM1) ( 17 ).…”

“…Our previous study used bioinformatics analysis and revealed that miR-152-3p was a cisplatin resistance-associated miRNA ( 17 ). The target genes of miR-152-3p were initially predicted using TargetScan and PicTar databases, which uncovered a binding site for miR-152-3p on the mRNA of neural cell adhesion molecule 1 (NCAM1) ( 17 ). However, the function of miR-152-3p in NSCLC and whether it is associated with DNMT-mediated methylation, as well as its regulatory mechanisms remain elusive.…”

An Overview of Long Non-Coding (lnc)RNAs in Neuroblastoma

“…In turn, FIRRE activates the WNT/β-catenin pathway, leading to an increase in cell proliferation and reduction of cell apoptosis [103]. Moreover, FIRRE upregulation was associated with shorter overall survival in kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, pancreatic adenocarcinoma, brain low-grade glioma, HCC and mesothelioma [104].…”