Abstract
BackgroundNon-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells along with metastasis in vivo, and to explore the underlying mechanism.MethodsRT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual-luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-5p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays.ResultsmiR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interact with STK32A to promote its expression. Following the validation of the supporting role of STK32A in NSCLC cells and NF-κB p65 phosphorylation, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo.ConclusionsmiR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A/NF-κB p65 axis, offering possible targets for the treatment for NSCLC.
Highlights
Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide
We looked up three thousand nucleotide sequences of serine/threonine kinase 32A (STK32A) in National Center for Biotechnology Information, predicted the promoter binding by http://jaspar.genereg.net/, and found the potential binding sites of Runt-related transcription factor 2 (RUNX2) to STK32A (Fig. 5a)
Through Chromatin immunoprecipitation (ChIP) experiments in A549 cells, we found that RUNX2 bound to STK32A promoter in STK32A-1 and STK32A-2 sites, but not in STK32A-3 or STK32A-4 sites
Summary
Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. MicroRNAs (miRNAs) are a group of small noncoding RNAs, which regulate the expression of genes at a posttranscriptional level and engage in many cellular processes involving cell growth, development as well as apoptosis [5]. These molecules have exerted great functions in cancer diagnostics, and their clinical potentials have been broadly studied in NSCLC [6]. MiR-196b inhibited growth and EMT of lung cancer cells by directly targeting RUNX2 [14]. Using a loss- and gain-of-function approach, we analyzed the role of the miR-130a-5p/RUNX axis in vitro and in vivo as well as the mechanism of action underlying
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have