Resumen de RUNX1-activated upregulation of lncRNA RNCR3 promotes cell proliferation, invasion, and suppresses apoptosis in colorectal cancer via miR-1301-3p/AKT1 axis in vitro and in vivo

H. Wang, G. Xu, D. Yuan, J. Yao, L. Meng, K. Li, Y. Zhang, C. Dang, K. Zhu

• Purpose Long non-coding RNAs (lncRNAs) have participated in progression of colorectal cancer. This study aims to study the role of RUNX1/RNCR3/miR-1301-3p/AKT1 axis in colorectal cancer.

  Methods The cancer tissues were from patients with colorectal cancer. The qRT-PCR was used to determine expression of lncRNA RNCR3, miR-1301-3p, and AKT1. Both dual-luciferase reporter assay and ChIP assay were conducted to investigate the binding sites of RUNX1 on RNCR3 promoter. Western blot was performed to analyze expression of AKT1 protein. Both dual-luciferase reporter assay and RIP assay were performed to detect the interacting sites between RNCR3 and miR-1301-3p. The CCK-8 assay, soft agar assay, transwell assay, and annexin-V-FITC/PI staining were applied to analyze the cell growth, invasion, and apoptosis, respectively.

  Results The data demonstrated that RNCR3 was elevated in colorectal cancer, and it was negatively correlated with expression of miR-1301-3p which was decreased in cancers. Then, RNCR3 could interact with and suppress miR-1301-3p expression in HCT116 and SW480. Knockdown of RNCR3 or miR-1301-3p overexpression significantly inhibited cell growth, invasion, and increased apoptosis through suppressing expression of Cyclin A1, PCNA, N-cadherin, Bcl-2, and promoting expression of E-cadherin, Bax in vitro and in vivo. RUNX1 was directly bound to RNCR3 promoter to activate RNCR3 expression. Furthermore, overexpression of RNCR3 blocked tumor inhibitory effects of miR-1301-3p on proliferation, colony formation, invasion, and apoptosis in vitro and in vivo. Additionally, RNCR3 and miR-1301-3p synergistically modulated AKT1 expression.

  Conclusion RUNX1-activated upregulation of RNCR3 promoted colorectal cancer progression by sponging miR-1301-3p to elevate AKT1 levels in vitro and in vivo.