CircANXA4 (hsa_circ_0055087) regulates the miR-1256/PRM1 axis to promote tumor progression in colorectal cancer.

Colorectal cancer (CRC) incidence ranks third among malignant cancers with a high propensity for distant metastasis. Despite continuous efforts to improve treatment, the prognosis especially in patients with advanced distant metastasis is low. The mechanism of development and progression of CRC is not fully understood. Non-coding RNAs (ncRNAs) have emerged as essential regulators in cancer progression. Here, we aim to dissect the role of one critical ncRNA, circANXA4, in CRC progression. CircANXA4 expression was analyzed by the GEO database. Differentially expressed circRNAs were identified by the Limma package R software. Expression of circANXA4 and miR-1256 was detected by qRT-PCR. The regulation of circANXA4 on cell proliferation and progression was confirmed with the cell viability assay using cell counting kit-8 (CCK-8) and transwell migration assay. RNA pull-down assay, RNA immunoprecipitation (RIP), and western blot were used to determine the interaction between circANXA4, miR-1256, and protamine1 (PRM1). CircANXA4 was upregulated in both CRC tissues and cell lines. Knockdown of circANXA4 effectively reduced cell proliferation, progression, and migration. Additionally, silencing circANXA4 remarkably increased miR-1256 expression, while reducing PRM1 expression, thereby demonstrating that circANXA4 downregulates miR-1256 expression through a complementary binding site. Rescue experiments revealed the interactions between circANXA4, miR-1256, and PRM1. Pearson correlation analysis revealed that circANXA4 expression positively correlated with PRM1 expression and miR-1256 expression inversely correlated with PRM1 expression. In sum, we demonstrated that circANXA4 promotes cancer cell proliferation and progression by sponging miR-1256 and upregulating PRM1 in CRC.

MiR-485-3p/MiR-543/MiR-337-3p is Required for the Oncogenic Potential of the Hsa_circ_0007385-MEMO1 Axis in Colorectal Cancer.

Circular RNAs (circRNAs) play regulatory roles in the biological processes of multiple tumors, colorectal cancer (CRC) included. Our previous study probed the impact of circ_0007385 on CRC cell malignant behaviors, while the underlying mechanism remains obscure. In this work, the potential mechanism of hsa_circ_0007385 in CRC was probed. Functional experiments were implemented for probing the function of hsa_circ_0007385 in CRC. Further analysis revealed the relation between hsa_circ_0007385 and miRNAs. A xenograft mouse model was implemented for probing the influence of hsa_circ_0007385 on CRC growth and metastasis in vivo. Hsa_circ_0007385 was up-regulated in CRC. Hsa_circ_0007385 positively regulated its host gene mediator of cell motility 1 (MEMO1). Hsa_circ_0007385 silencing inhibited CRC progression. Hsa_circ_0007385 and MEMO1 bond to miR-485-3p/miR-543/miR-337-3p, and these three miRNAs were lowly expressed in CRC, and negatively modulated by hsa_circ_0007385. Hsa_circ_0007385 functioned as an oncogene in CRC in a miR-485-3p/miR-543/miR-337-3p- or MEMO1-dependent manner. Hsa_circ_0007385 promoted CRC progression via modulating miR-485-3p/miR-543/miR-337-3p/MEMO1 axis. Thus, circ-MEMO1 might be a promising therapeutic target for CRC.