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.

Abstract

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.

• Authors: G Xu, H Wang, D Yuan, J Yao, L Meng, K Li, Y Zhang, C Dang, K Zhu
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 22 Issue 10 Pg. 1762-1777 (Oct 2020) ISSN: 1699-3055 [Electronic] Italy
• PMID: 32239427 (Publication Type: Journal Article)

Chemical References

• Core Binding Factor Alpha 2 Subunit
• MIRN1301 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• RUNX1 protein, human
• long non-coding RNA RNCR3, human
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (pathology)
• Core Binding Factor Alpha 2 Subunit (physiology)
• Disease Progression
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• MicroRNAs (physiology)
• Neoplasm Invasiveness
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-akt (physiology)
• RNA, Long Noncoding (genetics, physiology)
• Up-Regulation