Han Guohui, Bai Xiangdong, Jiang Hongchuan, He Qiang
Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Shanxi Medical University, Taiyuan, Shanxi 030013, P.R. China.
Department of Breast Surgery, Beijing Chaoyang Hospital, The Affiliated Hospital of Capital Medical University, Beijing 100020, P.R. China.
Exp Ther Med. 2021 Mar;21(3):235. doi: 10.3892/etm.2021.9666. Epub 2021 Jan 21.
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor outcome. The discovery that dysregulated microRNAs (miRNAs) play an important role in tumor progression has led to the suggestion that miRNAs (miRs) could be a potential target for the treatment of TNBC. In the present study, it was demonstrated that miR-598 expression was significantly decreased in TNBC tissues and was related to the degree of lymph node metastasis of patients with TNBC. Ectopic expression of miR-598 suppressed viability and colony formation, as well as increased the apoptosis of TNBC cells. To further understand the functional mechanism of action underlying miR-598 in TNBC, targets of miR-598 were predicted with the miRDB bioinformatics tool. Jagged 1 (JAG1) was identified as a direct target of miR-598, possessing a binding site for miR-598 in its 3'-untranslated region. Overexpression of miR-598 inhibited the expression of JAG1 in TNBC cells. In addition, JAG1 was highly expressed in TNBC tissues and its expression was negatively correlated with the expression of miR-598. Overexpression of JAG1 significantly attenuated the inhibitory effects of miR-598 on the proliferation and colony formation of TNBC cells. Collectively, these results provided novel insights into the functional mechanism of action for the miR-598/JAG1 pathway in the development of TNBC.
三阴性乳腺癌（TNBC）具有侵袭性表型且预后较差。失调的微小RNA（miRNA）在肿瘤进展中起重要作用这一发现，提示miRNA（miRs）可能是TNBC治疗的潜在靶点。在本研究中，结果表明miR-598在TNBC组织中的表达显著降低，且与TNBC患者的淋巴结转移程度相关。miR-598的异位表达抑制了细胞活力和集落形成，并增加了TNBC细胞的凋亡。为进一步了解miR-598在TNBC中的功能作用机制，使用miRDB生物信息学工具预测了miR-598的靶标。锯齿状蛋白1（JAG1）被鉴定为miR-598的直接靶标，其3'-非翻译区存在miR-598的结合位点。miR-598的过表达抑制了TNBC细胞中JAG1的表达。此外，JAG1在TNBC组织中高表达，其表达与miR-598的表达呈负相关。JAG1的过表达显著减弱了miR-598对TNBC细胞增殖和集落形成的抑制作用。总的来说，这些结果为miR-598/JAG1通路在TNBC发生发展中的功能作用机制提供了新的见解。
