Abstract
Circular RNAs (circRNAs) are a group of non-coding RNAs implicated in the pathogenesis of cancer progression, which exert their functions via regulation of microRNAs (miRNAs) and genes. The present study uses gain- and loss-of-function approaches to evaluate the functions of hsa_circRNA_002178 in angiogenesis along with energy metabolism and underlying downstream signals. The expression pattern of hsa_circRNA_002178 in clinical breast cancer tissues and its association with prognosis were characterized at first. Next, the energy metabolism and angiogenesis as well as cell viability were evaluated when the expression of hsa_circRNA_002178 in breast cancer cells was knocked down by siRNA. The interaction between hsa_circRNA_002178 and its downstream miR-328-3p was identified, followed by the analysis of their functions in regulation of breast cancer cellular behaviours. The target gene of miR-328-3p was predicted and verified, followed by identifying its role in the breast cancer progression. Higher expression of hsa_circRNA_002178 shared an association with worse prognosis in breast cancer. The inhibition of hsa_circRNA_002178 resulted in reductions in cell viability, energy metabolism and tube formation ability. Hsa_circRNA_002178 could competitively bind to miR-328-3p and down-regulated its expression. Restoration of miR-328-3p eliminated the tumour-promoting effects of hsa_circRNA_002178. COL1A1, as a target of miR-328-3p, could be up-regulated by overexpression of hsa_circRNA_002178. In vivo experiments further confirmed the inhibition of tumour growth and inflammation by silencing hsa_circRNA_002178 or up-regulating miR-328-3p. Taken together, hsa_circRNA_002178 is highlighted as a promising target for breast cancer due to the anti-tumour effects achieved by silencing hsa_circRNA_002178.
Keywords:
COL1A1; Hsa_circRNA_002178; MicroRNA-328-3p; angiogenesis; breast cancer; circular RNA; energy metabolism.