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

Abstract

Background: Circular 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.Methods: The 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.Results: CircRNA_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.Conclusions: CircRNA_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.

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

“…Therefore, it can be seen that circ-0000392 may become a potential clinical treatment target for CRC. 13 CircRUNX1 was derived from exons 2 and 3 of the RUNX1 gene, with a base sequence length of approximately 297 bp, and it is mainly located in the cytoplasm. As an oncogene, circRUNX1 was positively correlated with tumor staging, lymph node metastasis, and distant metastasis in CRC patients.…”

“…and biomarkers for CRC and promote great progress in the medical field of CRC treatment. [13][14][15][16] Circular RNAs (circRNAs) are a class of special noncoding RNA molecules formed from the 3' to 5' end rings of RNA that are highly expressed in the eukaryotic transcriptome. 17,18 Compared with linear RNAs, circRNAs have covalently closed circular structures without 5' cap structure and a 3' polyA tail and are much more stable than linear RNAs (with a half-life beyond 48 h), 13,17,19,20 which have a high degree of stability and potential effect on gene regulation.…”

“…[13][14][15][16] Circular RNAs (circRNAs) are a class of special noncoding RNA molecules formed from the 3' to 5' end rings of RNA that are highly expressed in the eukaryotic transcriptome. 17,18 Compared with linear RNAs, circRNAs have covalently closed circular structures without 5' cap structure and a 3' polyA tail and are much more stable than linear RNAs (with a half-life beyond 48 h), 13,17,19,20 which have a high degree of stability and potential effect on gene regulation. [21][22][23] In short, there is an urgent need to explore the source, classification, structural characteristics, and biological functions of circRNAs and a comprehensive understanding of the occurrence and development of CRC, chemotherapy resistance, recurrence and metastasis, and drug treatment targets and biomarkers.…”

circASS1 overexpression inhibits the proliferation, invasion and migration of colorectal cancer cells by regulating the miR‑1269a/VASH1 axis

“…Specifically, the role of circRNAs has been extensively investigated in multiple types of cancer (26)(27)(28). The unique characteristics of circRNAs highlight their potential as markers for the treatment of cancer (29). The tumor suppressive role of circASS1 in breast cancer has been previously reported (20).…”

Circular RNA circPRKDC promotes tumorigenesis of gastric cancer via modulating insulin receptor substrate 2 (IRS2) and mediating microRNA-493-5p

“…Recently, there is a heated discussion over the functions of circRNAs in different tumor progression [9]. For instance, circRNA_0000392 regulated the miR-193a-5p/PIK3R3/AKT pathway to accelerate colorectal cancer tumorigenesis [10]. Circ_POLA2 facilitated the malignant progression of lung cancer via elevating GNB1 by targeting miR-326 [11].…”