Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Cell Mol Med. 2020 Feb;24(3):2189-2201. doi: 10.1111/jcmm.14875. Epub 2020 Jan 19.
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.
环状 RNA（circRNA）是一组非编码 RNA，参与癌症进展的发病机制，通过调节 microRNA（miRNA）和基因发挥其功能。本研究使用增益和缺失功能方法来评估 hsa_circRNA_002178 在血管生成以及能量代谢和潜在下游信号中的功能。首先，描述了 hsa_circRNA_002178 在临床乳腺癌组织中的表达模式及其与预后的关系。接下来，当乳腺癌细胞中 hsa_circRNA_002178 的表达被 siRNA 敲低时，评估了能量代谢和血管生成以及细胞活力。鉴定了 hsa_circRNA_002178 与其下游 miR-328-3p 之间的相互作用，然后分析了它们在调节乳腺癌细胞行为中的功能。预测并验证了 miR-328-3p 的靶基因，然后确定了其在乳腺癌进展中的作用。hsa_circRNA_002178 的高表达与乳腺癌的预后不良有关。抑制 hsa_circRNA_002178 导致细胞活力、能量代谢和管形成能力降低。hsa_circRNA_002178 可以竞争性结合 miR-328-3p 并下调其表达。恢复 miR-328-3p 消除了 hsa_circRNA_002178 的促肿瘤作用。COL1A1 作为 miR-328-3p 的靶基因，可被 hsa_circRNA_002178 的过表达上调。体内实验进一步证实了沉默 hsa_circRNA_002178 或上调 miR-328-3p 抑制肿瘤生长和炎症的作用。总之，hsa_circRNA_002178 由于沉默 hsa_circRNA_002178 可实现抗肿瘤作用，因此被强调为乳腺癌的有前途的靶点。
