Research Paper|Volume 15, Issue 16|pp 8367—8383

The novel angiogenesis regulator circFAM169A promotes the metastasis of colorectal cancer through the angiopoietin-2 signaling axis

Zhiwei Wu^1,³, Fan Zhang¹, Shaobin Huang¹, Ming Luo¹, Kai Yang^1,²

¹Department of General Surgery, Changsha Central Hospital affiliated to University of South China, Changsha, Hunan 410000, China
²Department of General Surgery, the Third Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
³Department of Organ Transplantation Center, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China

* Equal contribution

Received: April 4, 2023Accepted: July 17, 2023Published: August 23, 2023

https://doi.org/10.18632/aging.204974

Copyright: © 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Angiogenesis plays an important role in the metastasis of cancers. However, the mechanisms whereby circular RNAs (circRNAs) regulate angiogenesis and affect cancer metastasis are still unclear.

Methods: We used gene set variation and Spearman’s correlation analyses to identify novel angiogenesis-related circRNAs, including circFAM169A. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used to assess the potential biological function of circFAM169A. A quantitative reverse transcription–PCR (qRT-PCR) analysis of 20 pairs of colorectal cancer (CRC) samples was performed to detect the expression level of circFAM169A. Transwell assays, tube formation assays, and nude mouse metastatic tumor models were used to study the function of circFAM169A in CRC. qRT-PCR, dual-luciferase reporter gene assay, RNA antisense purification assay, and Western blot were performed to analyze the competing endogenous RNA mechanism of circFAM169A in promoting CRC angiogenesis.

Results: circFAM169A was highly correlated with the hallmark of angiogenesis in CRC patients. It was up-regulated in liver metastasized CRC patients. circFAM169A overexpression promoted the angiogenesis, migration, and invasion of CRC cells while its down-regulation had the opposite effects. In vivo mouse models further highlighted the pro-metastatic role of circFAM169A in CRC. More importantly, we discovered that circFAM169A enhances the expression of angiopoietin-2 by binding to miR-518a-5p.