Circ_0030998 promotes tumor proliferation and angiogenesis by sponging miR-567 to regulate VEGFA in colorectal cancer

Longyang Jin,Tianyu Zhai,Chun Chen,Xiaoyu Zhang,Lei Lian,Chao Han

doi:10.1038/s41420-021-00544-7

Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Circular RNAs (circRNAs) are involved in pathological processes, especially in the development of cancers, but the roles of circRNAs in CRC are largely unknown. In this study, we investigated the role and underlying mechanisms of Circ_0030998 in CRC cell proliferation and angiogenesis. We found that Circ_0030998 was upregulated in CRC tissues and cells, and its upregulation was related to poor prognosis in CRC patients. Circ_0030998 promoted CRC cell proliferation in vitro and in vivo, and facilitated the angiogenesis of HUVECs. Mechanistic studies demonstrated that Circ_0030998 acted as a miR-567 sponge to relieve its inhibitory effect on VEGFA. Rescue assays validated that Circ_0030998 functioned in CRC cell proliferation and angiogenesis relying on VEGFA. Our findings clarified the Circ_0030998/miR-567/VEGFA regulation axis and indicated that Circ_0030998 could be a potential therapeutic target for CRC.

Highlights

Colorectal cancer (CRC), one of the most common malignancies, has become the third leading cause of cancer-related deaths worldwide [1]
To screen out the circRNA that may be related to the progression of CRC cells, the expression of 21 upregulated circRNAs was tested in CRC tissues, and it was shown that Circ_0030998 had the highest level than other 20 circRNAs
According to the circBase and UCSC Genome Browser Home, we found that Circ_0030998 was 220 base pairs in length located at chr13:113963957-113964177 and it was derived from the exon 3 of host gene LAMP1, which acted as an oncogene in the progression of several cancers [19, 20]

Summary

Introduction

Colorectal cancer (CRC), one of the most common malignancies, has become the third leading cause of cancer-related deaths worldwide [1]. It’s urgently needed to explore the molecular mechanisms related to the progression of CRC. About 1.5% of the human genome contains protein-coding genes, with the majority of the remaining transcribed into noncoding RNAs [4]. In terms of species complexity, noncoding genes may function more importantly than protein-coding genes [6]. More and more studies have shown that circRNAs are involved in pathological processes and could regulate gene expression in various ways [9]. CircRNAs could function as competing endogenous RNAs by sponging microRNAs to regulate gene expression. Some circRNAs could regulate the expression of host genes by interacting with RNA polymerase II [12]. The identification of more functional circRNAs may facilitate the molecularguided diagnosis and treatment of colorectal cancer

Methods

Results

Conclusion