RETRACTED ARTICLE: The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA

Chen Chen,Yanmin Song,Xiangmin Li,Xiaogang Li,Xiaoye Mo,Zhiguo Huang,Mu Zhang

doi:10.1186/s13046-020-01594-y

Abstract

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors globally. Angiogenesis is a key event maintaining tumor cell survival and aggressiveness. The expression of vascular endothelial growth factor A (VEGFA), one of the most significant tumor cell-secreted proangiogenic factors, is frequently upregulated in CRC.MethodsThe MTT assay was used to detect the viability of CRC cells. Transwell assays were performed to detect the invasion capacity of target cells. Relative protein levels were determined by immunoblotting. Pathological characteristics of tissues were detected by H&E staining and immunohistochemical (IHC) staining. A RIP assay was conducted to validate the predicted binding between genes.ResultsWe observed that circ-001971 expression was dramatically increased in CRC tissue samples and cells. Circ-001971 knockdown suppressed the capacity of CRC cells to proliferate and invade and HUVEC tube formation in vitro, as well as tumor growth in mice bearing SW620 cell-derived tumors in vivo. The expression of circ-001971 and VEGFA was dramatically increased whereas the expression of miR-29c-3p was reduced in tumor tissue samples. Circ-001971 relieved miR-29c-3p-induced inhibition of VEGFA by acting as a ceRNA, thereby aggravating the proliferation, invasion and angiogenesis of CRC. Consistent with the above findings, the expression of VEGFA was increased, whereas the expression of miR-29c-3p was decreased in tumor tissue samples. miR-29c-3p had a negative correlation with both circ-001971 and VEGFA, while circ-001971 was positively correlated with VEGFA.ConclusionsIn conclusion, the circ-001971/miR-29c-3p axis modulated CRC cell proliferation, invasion, and angiogenesis by targeting VEGFA.

Highlights

Colorectal cancer (CRC) is one of the most common malignant tumors globally
To identify circRNAs that might be related to CRC carcinogenesis, the top 11 upregulated circRNAs previously reported to be highly expressed in CRC tumor tissue samples compared with normal mucosa tissue samples (Table S2) [37], were selected for real-time polymerase chain reaction (PCR) confirmation
HCT116 and SW620 cells were transfected by miRNA mimics and examined for (f) the expression of circ-001971 by realtime PCR and (g) the expression of vascular endothelial growth factor A (VEGFA) by real-time PCR. miR-29c-3p was selected for further experiments. h miR-29c-3p inhibition was conducted in HCT116 and SW620 cells by the transfection of miR-29c-3p inhibitor

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant tumors globally. Angiogenesis is a key event maintaining tumor cell survival and aggressiveness. The expression of vascular endothelial growth factor A (VEGFA), one of the most significant tumor cell-secreted proangiogenic factors, is frequently upregulated in CRC. Angiogenesis can be found in numerous pathological processes, such as the development of most solid tumors [5], and acts as a critical factor in carcinogenesis [6]. Within isolated perfused organs the tumors did not become vascularized, but they did in mice [9]. Within tumorrelated practices, inhibition of angiogenesis, primarily by blocking the VEGF (vascular endothelial growth factor) family and the corresponding receptors, has been strongly confirmed to confer clinical benefits, and to prolong the overall survival of treated patients with specific types of diseases, including CRC [6]

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