Long non‑coding RNA LUCAT1 contributes to cisplatin resistance by regulating the miR‑514a‑3p/ULK1 axis in human non‑small cell lung cancer

Abstract

Drug resistance is a major obstacle in the therapy of malignant tumors, including non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in chemoresistance. The present study aimed to investigate the role of lung cancer-associated transcript 1 (LUCAT1) in cisplatin (DDP) resistance in NSCLC. By using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), it was found that the expression of LUCAT1 was elevated and that of microRNA-514a-3p (miR-514a-3p) was decreased in DDP-resistant NSCLC tissues and cells. Functionally, LUCAT1 upregulation enhanced cisplatin resistance by promoting the viability, autophagy and metastasis, and inhibiting the apoptosis of NSCLC cells, as demonstrated by Cell Counting kit-8 (CCK-8) assay, western blot analysis, Transwell assay and flow cytometric analysis. LUCAT1 was identified as a sponge of miR-514a-3p and uncoordinated-51-like kinase 1 (ULK1) was proven to be a target gene of miR-514a-3p by bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The enhancing effect of miR-514a-3p on cisplatin sensitivity was reversed by the elevation of LUCAT1. ULK1 knockdown suppressed cisplatin resistance, while this effect was attenuated by miR-514a-3p inhibition. Moreover, LUCAT1 positively regulated ULK1 expression by targeting miR-514a-3p. In addition, LUCAT1 knockdown suppressed tumor growth in vivo. On the whole, the findings of the present study demonstrate that LUCAT1 contributes to the resistance of NSCLC cells to cisplatin by regulating the miR-514a-3p/ULK1 axis, elucidating a novel regulatory network in cisplatin resistance in NSCLC.

PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation

“…PTENP1 is a pseudogene of known tumor suppressor PTEN and could decoy oncomiR including miR-17 and miR-20a to indirectly regulates ULK1 expression [ 27 ]. Similarly, LncRNAs, including PVT1, LUCAT1, SNHG6, and MALAT1, could indirectly regulate ULK1 expression through acting as microRNA sponge to regulate autophagy [ 28 – 31 ]. However, the direct regulation of ULK1 phosphorylation by LncRNAs has been hardly explored.…”

Roles of the Exosomes Derived From Myeloid-Derived Suppressor Cells in Tumor Immunity and Cancer Progression

“…Chemotherapy is one of the most important treatments for malignant tumors, but chemoresistance is a crucial obstacle impeding clinical treatment (124). At present, the mechanism underlying chemoresistance has not been well elucidated, but several emerging lines of evidence suggest that MDSCs induce reduced tumor cell sensitivity to chemotherapy.…”

Contribution of MicroRNAs in Chemoresistance to Cisplatin in the Top Five Deadliest Cancer: An Updated Review

“…A key initial event in autophagy is the formation of the autophagosome, and this step is mediated by the serine/threonine protein kinase ULK1 ( Zachari and Ganley, 2017 ). Mechanistically, ULK1 is targeted by miR-514a-3p in NSCLC cells ( Shen Q. et al, 2020 ). Moreover, miR-514a-3p was markedly downregulated in lung tissues and cells, and autophagy was found to be promoted ( Shen Q. et al, 2020 ).…”