Interference of the Circular RNA Sperm Antigen With Calponin Homology and Coiled-Coil Domains 1 Suppresses Growth and Promotes Apoptosis of Breast Cancer Cells Partially Through Targeting miR-1236-3p/Chromobox 8 Pathway

Abstract

Noncoding RNAs and RNA modifiers are implicated in cancer radiotherapy. Here, we aimed to investigate the role of sperm antigen with calponin homology and coiled-coil domains 1 (SPECC1)-derived circular RNA (circSPECC1; hsa_circ_0000745) in breast cancer (BC) cells under radiation treatment. Based on quantitative real-time PCR, circSPECC1 was highly upregulated in BC patients’ tumors and cells, and circSPECC1 expression was further increased with the dosage of radiation in BC cells. Moreover, circSPECC1 upregulation was found to be concomitant with higher chromobox 8 (CBX8) and lower microRNA (miR)-1236-3p expression. Functionally, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU) and colony formation assays showed that circSPECC1 interference suppressed cell proliferation and long-term survival in BC cells and irradiated BC cells. Xenograft tumor model experiments showed that circSPECC1 knockdown restrained BC tumor growth in vivo. Meanwhile, flow cytometry assay and western blotting revealed an enhanced apoptosis by silencing circSPECC1. Moreover, miR-1236-3p overexpression, similar to circSPECC1 silencing, displayed anti-growth and proapoptosis roles in irradiated BC cells. Mechanistically, dual-luciferase reporter assay and RNA immunoprecipitation assay identified a target relationship between miR-1236-3p and circSPECC1 or CBX8. Also, CBX8 expression could be modulated by circSPECC1 via miR-1236-3p regulation. Collectively, we indicated that inhibiting circSPECC1 could suppress growth and promote apoptosis of BC cells in both irradiated and nonirradiated conditions at least partially via miR-1236-3p/CBX8 axis, confirming that circSPECC1 might be target to develop anticancer drug in BC.