CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

Hanchen Xu,Yangxian Xu,Yujing Liu,Guang Ji,Chunyan Wang,Wenjun Zhou,Yang Liu,Peiqiu Cheng

doi:10.1186/s13046-020-01799-1

Abstract

BackgroundCircular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.MethodsThe expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.ResultsCircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.ConclusionsCircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.

Highlights

Circular RNAs, important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, in the malignant progression of cancer
We identified the Circular RNAs (circRNA) that can function as miRNA sponges from the significantly differentially expressed circRNAs and constructed a network map using Cytoscape software (Additional file 1: Fig. S3)
(See figure on previous page.) Fig. 1 Identification of circular RNAs by RNA-seq analyses in human colorectal cancer (CRC) samples. a The scatter plot shows the changes in circRNA expression in six paired CRC and adjacent normal tissues (ANT)

Summary

Introduction

Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. Circular RNAs (circRNAs) are important members of the noncoding RNA family along with microRNAs and lncRNAs. CircRNAs are characterized by their covalently closed loop structures and the absence of 3′ and 5′ ends. An increasing number of circRNAs have been identified in different tissues using high-throughput sequencing technology. Since most circRNAs are still not fully characterized and the roles of circRNAs in CRC progression are still largely unknown, further research is needed to identify the circRNAs associated with CRC tumorigenesis and to elucidate their functions

Methods

Results

Conclusion