Xu Jianfeng, Xu Siwei, Liu Weihui, Chen Jiabi, Cai Longbo, Zhuang Wei
Department of Urology, Jinjiang Municipal Hospital. No. 16, Luoshan Section, Jinguang Road, Luoshan Street, Jinjiang City, Quanzhou, Fujian, China.
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China.
J Cancer. 2024 Aug 19;15(16):5451-5461. doi: 10.7150/jca.99561. eCollection 2024.
Circular RNAs (circRNA) have a vital role in the progression of cancers. For instance, circTP63 is upregulated in prostate cancer (PCa) tissues compared with adjacent normal tissues. However, the role of circTP63 in prostate cancer is still unclear. qRT-PCR assays were applied to detected the expression of circTP63 and miR-421 in PCa samples. Functionally, CCK-8, apoptosis assay, and transwell migration and invasion assays were used to explore the role of circTP63 in PCa progression. Mechanistically, the interaction between circTP63 and miR-421 were verified using qRT-PCR and dual-luciferase report assay. Western blot, qRT-PCR, and dual-luciferase report assay were applied to detect the interaction between miR-421 and VAMP associated protein A (VAPA). And xenograft animal model was used to detect the role of circTP63 . circTP63 was upregulated and miR-421 was downregulated in PCa tissues. Functional assays revealed that circTP63 promoted the proliferation and metastasis of PCa cells . In addition, the inhibition effect of circTP63 knockdown could be rescued by miR-421 inhibition or VAPA overexpression. Mechanistically, circTP63-mediated PCa progression through directly binding to miR-421, and subsequently releasing the VAPA. silencing of circTP63 significantly impaired PCa progression. In summary, our study identified circTP63 as an oncogenic circRNA, which could be a promising diagnostic and therapeutic target for PCa treatment.
环状RNA（circRNA）在癌症进展中起着至关重要的作用。例如，与相邻正常组织相比，circTP63在前列腺癌（PCa）组织中上调。然而，circTP63在前列腺癌中的作用仍不清楚。应用qRT-PCR检测PCa样本中circTP63和miR-421的表达。在功能上，使用CCK-8、凋亡检测以及transwell迁移和侵袭检测来探究circTP63在PCa进展中的作用。在机制上，使用qRT-PCR和双荧光素酶报告检测验证circTP63与miR-421之间的相互作用。应用蛋白质免疫印迹法、qRT-PCR和双荧光素酶报告检测来检测miR-421与VAMP相关蛋白A（VAPA）之间的相互作用。并且使用异种移植动物模型来检测circTP63的作用。在PCa组织中，circTP63上调而miR-421下调。功能检测表明circTP63促进PCa细胞的增殖和转移。此外，circTP63敲低的抑制作用可通过miR-421抑制或VAPA过表达来挽救。在机制上，circTP63通过直接结合miR-421介导PCa进展，随后释放VAPA。circTP63的沉默显著损害PCa进展。总之，我们的研究确定circTP63为一种致癌性circRNA，它可能是PCa治疗中有前景的诊断和治疗靶点。
