Long non-coding RNA TP73-AS1 accelerates the progression and cisplatin resistance of non-small cell lung cancer by upregulating the expression of TRIM29 via competitively targeting microRNA-34a-5p

Abstract

Non-small cell lung cancer (NSCLC ) is a leading subtype of lung cancer, with high mortality rates. Recently, long non-coding RNA s (lncRNA s) have been associated with NSCLC . The present study aimed to examine the role of the TP73 antisense RNA 1 (TP73-A S1) lncRNA in NSCLC . TP73-A S1 and microRNA (miR)-34a-5p expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR ) and chromogenic in situ hybridization (CI SH). Cell proliferation, apoptosis, migration and invasion was determined using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Matrigel assays, respectively. The median inhibitory concentration (IC 50) value of cisplatin (cis-diamminedichloroplatinum; DD P) was assessed using a CC K-8 assay. The interaction between miR- 34a-5p and TP73-A S1 or tripartite motif-containing 29 (TRI M29) was predicted using microRNA . org and Starbase, then verified using a dual-luciferase reporter assay. The expression of TRIM29 was quantified at the mRNA and protein level using RT-qPCR and western blot analysis, respectively. TP73-AS1 was significantly upregulated, while miR- 34a-5p was downregulated in NSCLC tissues and cells. Functionally, TP73-A S1 knockdown inhibited proliferation, migration, invasion and DD P resistance, whilst inducing apoptosis in NSCLC cells. miR-34a-5p was identified as a target for TP73-A S1, and its inhibition reversed the effects of TP73-A S1 knockdown on NSCLC cells. In addition, TRI M29 was targeted by miR- 34a-5p, and its overexpression reversed the effects of miR- 34a-5p. Moreover, TP73-A S1 acted as a molecular sponge for miR- 34a-5p, increasing the expression of TRI M29. In conclusion, TP73-A S1 contributed to proliferation, migration and DD P resistance but inhibited apoptosis of NSCLC cells by upregulating TRI M29 and sponging miR- 34a-5p.