LncRNA BLACAT1 is involved in chemoresistance of non‑small cell lung cancer cells by regulating autophagy

Abstract

The aim of the present study was to determine the effect of the long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) in chemoresistance of non-small cell lung cancer (NSCLC) cells. Expression of lncRNA BLACAT1, microRNA (miR)-17, autophagy-related protein 7 (ATG7), multidrug-resistance protein 1 (MRP1), and the autophagy-associated proteins light chain 3 (LC3)-II/LC3-I and Beclin 1 were detected using the reverse transcription-quantitative polymerase chain reaction and western blot analysis. Cell viability was determined using an MTT assay. The interaction between BLACAT1 and miR-17 was determined using RNA immunoprecipitation and RNA pull-down assays. A cisplatin (DDP)-resistant NSCLC cell A549/DDP xenograft model in nude mice was established to investigate the effect of BLACAT1 on the chemoresistance of NSCLC cells. Compared with in DDP-sensitive NSCLC cells, expression of BLACAT1, ATG7, MRP1, LC3-II/LC3-I and Beclin 1 was significantly upregulated in DDP-resistant NSCLC cells, whereas miR-17 was downregulated in DDP-resistant NSCLC cells. Short interfering RNA against BLACAT1 decreased the viability of DDP-resistant NSCLC cells. In addition, BLACAT1 interacted with miR-17, and negatively regulated miR-17. BLACAT1 promoted ATG7 expression through miR-17, and facilitated autophagy and promoted chemoresistance of NSCLC cells through miR-17/ATG7. Finally, in vivo experiments indicated that inhibition of BLACAT1 ameliorated the chemoresistance of NSCLC. BLACAT1 was upregulated in DDP-resistant NSCLC cells, and promoted autophagy and chemoresistance of NSCLC cells through the miR-17/ATG7 signaling pathway.

Long noncoding RNA PART1 promotes progression of non‐small cell lung cancer cells via JAK‐STAT signaling pathway

“…NSCLC is a widespread metastases and poor prognosis tumor . Recent studies have shown that various types of lncRNAs, such as TBILA, NNT‐AS1, BLACAT1, exhibited biological functions and were involved in the progression of NSCLC. Moreover, although PART1 was upregulated in NSCLC specimens with poor prognosis, the detailed functional role of PART1 in the pathogenesis of NSCLC remains under‐investigated.…”

Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

“…Similarly, lncRNA-XIST can reduce DDP efficacy in tumor cells via the lncRNA-XIST/miR-17/autophagy regulatory axis and the let-7i/BAG-1 axis by decreased apoptosis and increased proliferation [38,39]. Moreover, it has been reported that lncRNA bladder cancerassociated transcript 1 (BLACAT1) is upregulated in DDP-resistant NSCLC cells and promotes autophagy and chemoresistance via the miR-17/autophagy-related 7 (ATG7) signaling pathway [40]. LncRNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (lncRNA NNT-AS1) is remarkably expressed in DDP-resistant NSCLC tissues and cells, and overexpression of lncRNA NNT-AS1 can alter cell proliferation, cell cycle and apoptosis through the mitogen-activated protein kinase (MAPK)/Slug signaling pathway [41].…”

Potential role of exosomes in cancer therapy

“…Lung cancer is the leading cause of cancer mortality worldwide, with annually 2.1 million global deaths, and the 5‐year relative survival rate of lung cancer only accounts for 18% . Chemotherapy is effective in triggering the death of tumor cells; however, the occurrence of drug resistance can limit its efficacy in lung cancer …”

“…20 Chemotherapy is effective in triggering the death of tumor cells; however, the occurrence of drug resistance can limit its efficacy in lung cancer. 21 Exosomal miRNAs play important roles in lung cancer chemoresistance. A previous study reported that exosomal miR-425-3p decreases the responsiveness to cisplatin (DDP) in PC-9 and SPCA1 cells, in which the molecular mechanism underlying the role of miR-425-3p involves AKT1.…”