Cai Yujie, Zhao Xing, Chen Danze, Zhang Fan, Chen Qiuyang, Shao Chang-Chun, Ouyang Yan-Xiu, Feng Jun, Cui Lili, Chen Min, Xu Jianzhen
Systems Biology Lab, Shantou University Medical College (SUMC), 515041 Shantou, China.
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, 524000 Zhanjiang, China.
Mol Ther Nucleic Acids. 2021 Oct 1;26:773-786. doi: 10.1016/j.omtn.2021.09.013. eCollection 2021 Dec 3.
Circular RNAs (circRNAs) play important roles in carcinogenesis. Here, we investigated the mechanisms and clinical significance of , a highly repressed circRNA in breast cancer. Subsequently, we also identified RNA-binding proteins (RBPs) that regulate . Bioinformatics analysis was utilized to predict regulatory RBPs as well as downstream microRNAs (miRNAs) and mRNA targets. RNA immunoprecipitation, luciferase assay, fluorescence hybridization, cell proliferation, wound healing, Matrigel invasion, cell apoptosis assays, and a xenograft model were used to investigate the function and mechanisms of and . The clinical value of was evaluated in a large cohort of breast cancer by quantitative real-time PCR. is downregulated in breast cancer and associated with aggressive characteristics and shorter survival time. Upregulation of promotes apoptosis, decreases proliferation, and inhibits invasion and migration. Furthermore, binds multiple miRNAs to alleviate carcinogenesis by regulating PDCD4. CASC3 and metadherin (MTDH) can bind directly to with characterized motifs. Accordingly, ectopic expression or depletion of CASC3 or MTDH leads to expression changes, suggesting that these two RBPs modulate in cancer cells. is a novel biomarker for diagnosis and prognosis in breast cancer. These results highlight the importance of therapeutic targeting of the RBP-noncoding RNA (ncRNA) regulation network.
环状RNA（circRNAs）在肿瘤发生过程中发挥重要作用。在此，我们研究了一种在乳腺癌中高度抑制的环状RNA——[具体名称未给出]的作用机制及临床意义。随后，我们还鉴定了调控[具体名称未给出]的RNA结合蛋白（RBPs）。利用生物信息学分析预测调控性RBPs以及[具体名称未给出]下游的微小RNA（miRNAs）和mRNA靶点。通过RNA免疫沉淀、荧光素酶报告基因检测、荧光原位杂交、细胞增殖、伤口愈合、基质胶侵袭、细胞凋亡检测以及异种移植模型来研究[具体名称未给出]的功能和机制。通过定量实时PCR在一大群乳腺癌患者中评估[具体名称未给出]的临床价值。[具体名称未给出]在乳腺癌中表达下调，且与侵袭性特征及较短生存时间相关。上调[具体名称未给出]可促进细胞凋亡、降低细胞增殖，并抑制侵袭和迁移。此外，[具体名称未给出]通过调节程序性细胞死亡蛋白4（PDCD4）与多种miRNAs结合以减轻肿瘤发生。CASC3和黏附素（MTDH）可通过特定基序直接与[具体名称未给出]结合。因此，异位表达或敲低CASC3或MTDH会导致[具体名称未给出]表达变化，表明这两种RBPs在癌细胞中调节[具体名称未给出]。[具体名称未给出]是乳腺癌诊断和预后的新型生物标志物。这些结果凸显了靶向RBP-非编码RNA（ncRNA）调控网络进行治疗的重要性。
