Qian Fan1, Xiuting Hu2, Haiyang Zhang1, Shengguang Wang1, Huilai Zhang1, Chaoying You1, Chen-Yu Zhang2, Hongwei Liang2, Xi Chen2, Yi Ba1. 1. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China. 2. State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Abstract
BACKGROUND/AIMS: MicroRNAs (miRNAs) have emerged as major regulators of tumour development and progression in non-small cell lung cancer (NSCLC). However, the role of miR-193a-3p in NSCLC is still unclear. METHODS: Quantitative RT-PCR was used to detect miR-193a-3p expression levels in NSCLC tumour tissues. CCK8, EdU and cell migration assays were performed to analyse the biological functions of miR-193a-3p in NSCLC cells. Luciferase reporter assays were used to validate the bioinformatics-predicted target genes of miR-193a-3p. Western blotting and RNA/DNA interference carried out to evaluate the association between miR-193a-3p and KRAS. RESULTS: miR-193a-3p expression was decreased in the NSCLC tumour tissues. We investigated the biological effects of miR-193a-3p both in vivo and in vitro and found that enforced expression of miR-193a-3p inhibited tumour formation and suppressed cell proliferation and cell migration. KRAS was found to be a potential target of miR-193a-3p, and dual luciferase reporter assays showed that miR-193a-3p directly binds to the 3'-untranslated region (3'-UTR) of KRAS mRNA. In addition, we found that changing the expression of KRAS had the opposite results to those induced by miR-193a-3p in the NSCLC cells. Importantly, simultaneous overexpression of miR-193a-3p and KRAS could counteract the effects of both on cellular functions. CONCLUSION: These findings highlight an important role for miR-193a-3p as a tumour suppressor in NSCLC pathogenesis via the regulation of KRAS expression.
BACKGROUND/AIMS: MicroRNAs (miRNAs) have emerged as major regulators of tumour development and progression in non-small cell lung cancer (NSCLC). However, the role of miR-193a-3p in NSCLC is still unclear. METHODS: Quantitative RT-PCR was used to detect miR-193a-3p expression levels in NSCLC tumour tissues. CCK8, EdU and cell migration assays were performed to analyse the biological functions of miR-193a-3p in NSCLC cells. Luciferase reporter assays were used to validate the bioinformatics-predicted target genes of miR-193a-3p. Western blotting and RNA/DNA interference carried out to evaluate the association between miR-193a-3p and KRAS. RESULTS: miR-193a-3p expression was decreased in the NSCLC tumour tissues. We investigated the biological effects of miR-193a-3p both in vivo and in vitro and found that enforced expression of miR-193a-3p inhibited tumour formation and suppressed cell proliferation and cell migration. KRAS was found to be a potential target of miR-193a-3p, and dual luciferase reporter assays showed that miR-193a-3p directly binds to the 3'-untranslated region (3'-UTR) of KRAS mRNA. In addition, we found that changing the expression of KRAS had the opposite results to those induced by miR-193a-3p in the NSCLC cells. Importantly, simultaneous overexpression of miR-193a-3p and KRAS could counteract the effects of both on cellular functions. CONCLUSION: These findings highlight an important role for miR-193a-3p as a tumour suppressor in NSCLC pathogenesis via the regulation of KRAS expression.
Authors: Yong Cui; Qi Wang; Jing Lin; Lei Zhang; Chi Zhang; Huairui Chen; Jun Qian; Chun Luo Journal: Front Oncol Date: 2021-04-23 Impact factor: 6.244