Chen Dong, Lu Xinxing, Yang Feiya, Xing Nianzeng
Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Department of Urology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing 100021, China,
Cancer Manag Res. 2019 Feb 12;11:1415-1423. doi: 10.2147/CMAR.S190669. eCollection 2019.
While emerging evidence indicates that circHIPK3 is critically involved in tumorigenesis and the development of several cancers, its role in prostate cancer (PCa) is not clearly understood.
Human PCa samples and their matched normal adjacent tissues were obtained from 26 patients to assess the expression of circHIPK3 and its relationship with PCa prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circHIPK3 in PCa progression and its underlying molecular mechanisms.
In this study, we found that circHIPK3 was overexpressed in PCa tissues and that higher circHIPK3 expression was associated with tumor stage. Moreover, circHIPK3 knockdown markedly inhibited the proliferation, migration, and invasion of PCa cells in vitro and impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrated that circHIPK3 could promote MCL1 expression by interacting with miR-193a-3p in PCa. Finally, rescue assays illustrated that circHIPK3 knockdown could partially reverse the effects of MCL1 overexpression.
In summary, our study illustrated, for the first time, that circHIPK3-mediated miR-193a-3p-MCL1 signaling promotes PCa development and progression, providing a novel therapeutic target for PCa.
虽然新出现的证据表明环状HIPK3在肿瘤发生和多种癌症的发展中起关键作用，但其在前列腺癌（PCa）中的作用尚不清楚。
从26例患者中获取人前列腺癌样本及其匹配的正常相邻组织，以评估环状HIPK3的表达及其与前列腺癌预后的关系。进行了一系列体外和体内功能实验，以阐明环状HIPK3在前列腺癌进展中的作用及其潜在的分子机制。
在本研究中，我们发现环状HIPK3在前列腺癌组织中过表达，且较高的环状HIPK3表达与肿瘤分期相关。此外，环状HIPK3敲低显著抑制了前列腺癌细胞在体外的增殖、迁移和侵袭，并损害了体内肿瘤生长。生物信息学分析和荧光素酶报告基因检测表明，环状HIPK3可通过与前列腺癌中的miR-193a-3p相互作用来促进MCL1表达。最后，挽救实验表明环状HIPK3敲低可部分逆转MCL1过表达的作用。
总之，我们的研究首次表明，环状HIPK3介导的miR-193a-3p-MCL1信号通路促进前列腺癌的发展和进展，为前列腺癌提供了一个新的治疗靶点。
