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环状ROBO1通过加速糖酵解促进前列腺癌生长和恩杂鲁胺耐药。

circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis.

作者信息

Zhou Zhigang, Qin Jing, Song Cailu, Wu Tao, Quan Qiang, Zhang Yan, Zou Yani, Liu Lingrui, Tang Hailin, Zhao Jianfu

机构信息

Research Center of Cancer Diagnosis and Therapy, Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.

Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, China.

出版信息

J Cancer. 2023 Aug 21;14(13):2574-2584. doi: 10.7150/jca.86940. eCollection 2023.

Abstract

As non-coding RNAs, circular RNAs (circRNAs) contribute to the progression of malignancies by regulating various biological processes. In prostate cancer, however, there is still a lack of understanding regarding the potential molecular pathways and roles of circRNAs. Loss-off function experiments were performed to investigate the potential biological function of circRNA in the progression of prostate cancer. Western blot, qRT-PCR, and IHC assay were used to examine the expression level of different genes or circRNAs. Further molecular biology experiments were conducted to uncover the molecular mechanism underlying circRNA in prostate cancer using dual luciferase reporter and RNA immunoprecipitation (RIP) assays. A novel circRNA (hsa_circ_0124696, named circROBO1) was identified as a significantly upregulated circRNA in both prostate cancer cells and tissues. Suppression of circROBO1 significantly attenuated the proliferation of prostate cancer cells. In addition, we found that the knockdown of circROBO1 remarkably increased the sensitivity of prostate cancer to enzalutamide treatment. A deceleration in glycolysis rate was observed after inhibition of circROBO1, which could suppress prostate cancer growth and overcome resistance to enzalutamide. Our results revealed that circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis. Our study identified the biological role of the circROBO1-miR-556-5p-PGK1 axis in the growth and enzalutamide resistance of prostate cancer, which is the potential therapeutic target of prostate cancer.

摘要

作为非编码RNA,环状RNA(circRNA)通过调节各种生物学过程促进恶性肿瘤的进展。然而,在前列腺癌中,对于circRNA的潜在分子途径和作用仍缺乏了解。进行功能缺失实验以研究circRNA在前列腺癌进展中的潜在生物学功能。使用蛋白质免疫印迹法、定量逆转录聚合酶链反应和免疫组化分析来检测不同基因或circRNA的表达水平。使用双荧光素酶报告基因和RNA免疫沉淀(RIP)分析进行进一步的分子生物学实验,以揭示前列腺癌中circRNA的分子机制。一种新型circRNA(hsa_circ_0124696,命名为circROBO1)被鉴定为在前列腺癌细胞和组织中均显著上调的circRNA。抑制circROBO1可显著减弱前列腺癌细胞的增殖。此外,我们发现敲低circROBO1可显著提高前列腺癌对恩杂鲁胺治疗的敏感性。抑制circROBO1后观察到糖酵解速率减慢,这可以抑制前列腺癌生长并克服对恩杂鲁胺的耐药性。我们的结果表明,circROBO1通过加速糖酵解促进前列腺癌生长和恩杂鲁胺耐药。我们的研究确定了circROBO1-miR-556-5p-PGK1轴在前列腺癌生长和恩杂鲁胺耐药中的生物学作用,这是前列腺癌的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/896f/10475366/231255fad9b0/jcav14p2574g001.jpg

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