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
MOLECULAR MEDICINE REPORTS(2020)
Abstract
Non-small cell lung cancer (NSCLC) is a leading subtype of lung cancer, with high mortality rates. Recently, long non-coding RNAs (lncRNAs) have been associated with NSCLC. The present study aimed to examine the role of the TP73 antisense RNA 1 (TP73-AS1) lncRNA in NSCLC. TP73-AS1 and microRNA(miR)-34a-5p expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR) and chromogenicin situhybridization (CISH). 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 (IC50) value of cisplatin (cis-diamminedichloroplatinum; DDP) was assessed using a CCK-8 assay. The interaction between miR-34a-5p and TP73-AS1 or tripartite motif-containing 29 (TRIM29) was predicted usingmicroRNA.organd 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-AS1 knockdown inhibited proliferation, migration, invasion and DDP resistance, whilst inducing apoptosis in NSCLC cells. miR-34a-5p was identified as a target for TP73-AS1, and its inhibition reversed the effects of TP73-AS1 knockdown on NSCLC cells. In addition, TRIM29 was targeted by miR-34a-5p, and its overexpression reversed the effects of miR-34a-5p. Moreover, TP73-AS1 acted as a molecular sponge for miR-34a-5p, increasing the expression of TRIM29. In conclusion, TP73-AS1 contributed to proliferation, migration and DDP resistance but inhibited apoptosis of NSCLC cells by upregulating TRIM29 and sponging miR-34a-5p.
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Key words
tumor protein 73 antisense RNA 1,miR-34a-5p,tripartite motif-containing 29,cisplatin resistance,non-small cell lung cancer
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