Circular RNA circCTNNA1 promotes colorectal cancer progression by sponging miR-149-5p and regulating FOXM1 expression

Abstract

Circular RNAs (circRNAs) are an emerging class of non-coding RNAs, identified to participate in multiple malignancies. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in colon cancer (CC) remain largely unclear. In this study, the circRNA expression profile in CC and matched normal tissues was analyzed using circRNA microarrays. A novel circRNA, circCTNNA1, was significantly upregulated in CC, and its level was associated with advanced tumor–node–metastasis stage and poor prognosis of patients with CC. Functional experiments, including Cell Counting Kit-8, colony formation, 5‐ethynyl‐2′‐deoxyuridine, transwell, wound healing, flow cytometric analysis, and in vivo tumorigenesis assay were then performed to investigate the oncogenic role of circCTNNA1. The results revealed that circCTNNA1 promoted CC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual-luciferase reporter assays, and fluorescent in situ hybridization were performed to unveil that circCTNNA1 can serve as a competing endogenous RNA of miR-149-5p to counteract the suppressive effect of miR-149-5p on downstream target Forkhead Box M1 (FOXM1). In summary, our study demonstrated that circCTNNA1 facilitated CC proliferation and invasion via the circCTNNA1/miR-149-5p/FOXM1 axis, and it might function as a novel diagnostic or therapeutic target for patients with CC.

CircCTNNA1 acts as a ceRNA for miR-363-3p to facilitate the progression of colorectal cancer by promoting CXCL5 expression

“…In vivo experiments suggested that downregulated circCTNNA1 had a significant inhibitory effect on CRC tumorigenesis. Based on the above results, we believed that circCTNNA1 played a positive role in the progression of CRC, which was consistent with the results of previous studies [ 17 ]. In addition, we found a significant positive correlation between circCTNNA1 expression and CXCL5 expression in CRC tissues.…”

“…In the previous study, Chen et al . found that circCTNNA1 was an upregulated circRNA in CRC tissues, which could accelerate CRC proliferation and metastasis [ 17 ]. Therefore, circCTNNA1 might be a potential target of CRC.…”

Mechanism of circADD2 as ceRNA in Childhood Acute Lymphoblastic Leukemia

“…For example, circCCDC9 sponges miR-6792-3p to suppress the progression of gastric cancer through up regulating CAV1 expression ( Luo et al, 2020 ). In another example, circCTNNA1 promotes colorectal cancer progression via circCTNNA1/miR-149-5p/FOXM1 axis ( Chen et al, 2020 ). Also, circSLC8A1 plays a suppressive role in bladder cancer progression via sponging miR-130b/miR-494 and upregulating downstream PTEN ( Lu et al, 2019 ).…”

Circular RNA circCTNNA1 is downregulated in osteoarthritis and sponges miR-29a to suppress LPS-induced apoptosis of synoviocytes

“…CircCTNNA1 has been characterized as a critical player in colorectal cancer (13). It is reported that circCTNNA1 is overexpressed in colorectal cancer, and it upregulate FOXM1 by sponging miR-149-5p to promote cancer progression (13). However, the role of circCTNNA1 in other human disease is unknown.…”

“…However, the role of most circRNAs in OA is unknown. CircRNA circCTNNA1 has been characterized as a critical player in cancer biology (13), while its role in other human diseases is unknown. We performed bioinformatics analysis and found that circCTNNA1 could interact with miR-29a, which is a crucial player in the apoptosis of synoviocytes (14).…”