<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

Abstract

Purpose: Recently, studies have demonstrated that a novel circular RNA (circRNA), circMAT2B, can promote cell proliferation and can thus contribute to the growth and development of hepatocellular carcinoma. However, the precise mechanisms underlying in circMAT2B-induced colorectal cancer (CRC) cell proliferation are not yet fully understood. Materials and Methods: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circMAT2B expression in 70 CRC tissues and 70 matched adjacent normal tissues, CRC cell lines and human colonic epithelial cell line (NCM460). The direct interaction between miR-610 and circMAT2B or E2F1 was verified using luciferase reporter assay and biotinylated RNA Pull-down assay. Cell Counting Kit-8, colony formation assay, flow cytometry were utilized to examine the effect of circMAT2B, miR-610 and E2F1 on cell proliferation. Western blot was conducted to evaluate E2F1 expression. Results: In our study, circMAT2B was found to be upregulated in CRC tissues and cell lines. Furthermore, the silencing of circMAT2B significantly inhibited proliferation. Hence, in order to investigate the mechanism underlying the oncogenic properties of circMAT2B in CRC, a bioinformatics analysis (circular RNA Interactome, https://circinteractome.nia.nih. gov/) was performed to screen the putative interacting microRNAs of circMAT2B. miR-610 was identified to be one of the potential targeted miRNAs of circMAT2B. Luciferase reporter and RNA pulldown assay confirmed a direct interaction between circMAT2B and miR-610. Moreover, circMAT2B expression was negatively correlated with the expression of miR-610 in CRC tissues (r=−0.5131, p<0.0001). Furthermore, we demonstrated circMAT2B upregulated expression levels of the miR-610 target gene E2F1, which is involved in cell proliferation, is overexpression in a broad range of human cancer including CRC. Further studies suggested that E2F1 upregulation could significantly reverse the si-circMAT2B-mediated inhibition of proliferation. Conclusion: circMAT2B is upregulated in CRC tissues and cell lines. Moreover, circMAT2B promoted CRC proliferation by regulating the miR-610/E2F1 axis, which may serve as a potential therapeutic target for CRC treatment.

lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway

“…The database predicted that NEAT1 binds to transcription factor E2F1, and E2F1 binds to KDM5A. E2F1, a crucial molecule implicated in cell proliferation and apoptosis, is overexpressed in a broad range of human cancers, including CRC (39,40). An elevated E2F1 expression in cancer cells can induce metastasis and invasion (41), as well as enhance the aggressiveness of CRC (42).…”

An Update on the Potential Roles of E2F Family Members in Colorectal Cancer

“…For example, MAT2B, a novel circRNA, was found to increase E2F1 expression through sponging miR-610, resulting in tumorigenesis or further development. 20 Similarly, cir_001569 upregulates E2F5 by sponging miR-145 and is correlated with the aggressive character of CRC. 21 Furthermore, the circCAMSAP1/miR-328-5p/E2F1 axis is also essential for CRC progression.…”

Hsa_circ_0003945 promotes progression of hepatocellular carcinoma by mediating miR‐34c‐5p/LGR4/β‐catenin axis activity

“…Although accumulating research has revealed that circRNAs clearly show abnormal expression related to tumour growth and progression in HCC, 17,28‐30 the function of numerous circRNAs in HCC remains elusive and needs to be further investigated. In the current study, the expression of Circ_0003945, originating from exon 11 and 12 of UBAP2, was significantly upregulated in HCC tissue and plasma.…”