Huang Yixiang, Zheng Wenfang, Ji Changle, Wang Xuehui, Yu Yunhe, Deng Xiaochong, Zhou Xiqian, Fang Lin
Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Cell Death Discov. 2021 Dec 6;7(1):376. doi: 10.1038/s41420-021-00771-y.
Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3'-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.
乳腺癌(BC)是全球女性中最致命的疾病之一。据报道,包括环状RNA(circRNAs)在内的非编码RNA在肿瘤发生和发展的不同方面发挥作用。在本研究中,我们旨在探讨circRPPH1在乳腺癌中的生物学功能及潜在机制。从基因表达综合数据库(GEO)的数据集GSE101123中筛选候选circRNAs,发现一种差异表达的circRNA,即circRPPH1,在乳腺癌中表达上调。与配对的癌旁组织相比,circRPPH1在癌组织中的表达更高。进一步的体外和体内实验表明,circRPPH1在乳腺癌中起癌基因作用。此外,circRPPH1主要定位于细胞质中,发挥miR-512-5p海绵的作用。通过从STAT1的3'-UTR中隔离miR-512-5p,circRPPH1抑制了miR-512-5p的抑制作用,稳定了乳腺癌中STAT1的mRNA,最终影响乳腺癌的进展。总之,这些发现表明circRPPH1作为一种癌基因,通过circRPPH1-miR-512-5p-STAT1轴调节乳腺癌的进展,这可能为乳腺癌治疗提供一个潜在的治疗靶点。