CircRNA DNA methyltransferase 1 silence inhibits breast cancer development by regulating micoRNA‐485‐3p/zinc finger E‐box binding homeobox 1 axis

Abstract

Background Circular RNAs (circRNAs) are associated with tumorigenesis of breast cancer. Nevertheless, how and whether circRNA DNA methyltransferase 1 (circ‐DNMT1) controls breast cancer development remains poorly understood. Methods The paired tumor and paracancer tissues (n = 41) were obtained from breast cancer patients. Circ‐DNMT1, microRNA (miR)‐485‐3p, and zinc finger E‐box binding homeobox 1 (ZEB1) abundances were measured by quantitative reverse transcription polymerase chain reaction and western blot. Cell colony formation, migration, invasion, and apoptosis were analyzed by colony formation analysis, transwell analysis, and flow cytometry. Target relationship was evaluated via dual‐luciferase reporter analysis, RNA immunoprecipitation, and pull‐down. The in vivo experiments were conducted using a xenograft model. Results Circ‐DNMT1 and ZEB1 levels were upregulated in breast cancer, and miR‐485‐3p was downregulated. Circ‐DNMT1 knockdown restrained cell colony formation, migration, and invasion and increased apoptosis. MiR‐485‐3p was negatively regulated by circ‐DNMT1, and miR‐485‐3p knockdown mitigated the effect of circ‐DNMT1 silence on breast cancer development. ZEB1 was targeted via miR‐485‐3p, miR‐485‐3p overexpression repressed cell colony formation, migration, and invasion and triggered apoptosis by decreasing ZEB1. Circ‐DNMT1 silence reduced ZEB1 expression via regulating miR‐485‐3p. Circ‐DNMT1 knockdown reduced xenograft tumor growth. Conclusion Circ‐DNMT1 knockdown constrains breast cancer development via modulating miR‐485‐3p/ZEB1 axis.

circDNMT1 Promotes Malignant Progression of Gastric Cancer Through Targeting miR-576-3p/Hypoxia Inducible Factor-1 Alpha Axis

“…circDNMT1 was overexpressed in breast cancer tissues. As an miRNA sponge, circDNMT1 maintains the highly proliferative state of breast cancer by regulating the miR-485-3p/ZEB1 axis ( 20 ). Another study showed that circDNMT1 promotes nuclear translocation of p53 and AUF1 and activates autophagy to increase survival capabilities of breast cancer ( 19 ).…”

“…Hsa_circ_0049224 (circDNMT1) is a newly identified circRNA in cancer treatment. It has been reported to be an autophagy modifier and miRNA sponge that potentiates breast cancer development ( 19 , 20 ). Since the biological functions of circDNMT1 in GC remain unknown, in this study, we aimed to explore the role and underlying mechanisms of circDNMT1 in GC.…”

Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy

“…Compared to miR-1246, fewer investigations have addressed the role of miR-485-3p in cancer, but, with few exceptions [ 65 , 66 , 67 ], it appears to function as a tumor-suppressor miRNA. Its expression in tumor tissue was found to be downregulated in prostate cancer [ 68 , 69 ], glioblastoma [ 70 ], breast and colorectal cancer [ 71 , 72 , 73 , 74 ], osteosarcoma [ 75 ] and renal carcinoma [ 76 ]. Interestingly, in some of those studies, the reduced expression of miR-485-3p was linked to upregulation of a long non-coding RNA (LncRNA) [ 75 ] or a circular RNA [ 72 , 74 , 76 ] able to sponge the miRNA, thus leading to enhanced expression of target genes promoting tumor cell proliferation, survival and invasiveness.…”

“…Its expression in tumor tissue was found to be downregulated in prostate cancer [ 68 , 69 ], glioblastoma [ 70 ], breast and colorectal cancer [ 71 , 72 , 73 , 74 ], osteosarcoma [ 75 ] and renal carcinoma [ 76 ]. Interestingly, in some of those studies, the reduced expression of miR-485-3p was linked to upregulation of a long non-coding RNA (LncRNA) [ 75 ] or a circular RNA [ 72 , 74 , 76 ] able to sponge the miRNA, thus leading to enhanced expression of target genes promoting tumor cell proliferation, survival and invasiveness. In the circulation, lower levels of miR-485-3p were detected in serum and serum exosome of glioblastoma patients as compared with healthy subjects [ 77 , 78 ].…”

Role of DNA Methyltransferases (DNMTs) in metastasis

“…Circ-DNMT1 interfered with miR-485-3p-induced targeting of ZEB1. There was an evident reduction in the tumor growth in mice inoculated with circ-DNMT1-silenced-MDA-MB-231 cancer cells (61).…”