Zhang Heyuan, Chen Nanhui, Deng Zhihai, Mai Yang, Deng Limin, Chen Guo, Li Yutong, Pan Bin, Zhong Weifeng
Department of Urology, Meizhou People's Hospital (Huangtang Hospital), Meizhou, China.
Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People's Hospital (Huangtang Hospital), Meizhou, China.
Front Genet. 2021 Sep 3;12:687236. doi: 10.3389/fgene.2021.687236. eCollection 2021.
Prostate cancer (PCa) is a serious disease that affects men's health. To date, no effective and long-lasting treatment option for this condition is available in clinical practice. ANT2 is highly expressed in a variety of hormone-related cancers, but its relationship and regulatory mechanism with PCa are unclear. In this study, we found that ANT2 expression was significantly upregulated in PCa tissues relative to control samples. Genetic knockdown of ANT2 effectively inhibited, while overexpression promoted, proliferation, migration, and invasion of PCa cells. In addition, miR-137 expression was reduced in prostate cancer tissues relative to control tissues. We identified a regulatory site for miR-137 in the 3'-UTR of ANT2 mRNA; luciferase reporter assays indicated that ANT2 is a direct target gene for miR-137. Transfecting cells with miR-137 mimics and/or an ANT2-encoding plasmid revealed that ANT2 promotes proliferation, migration, and invasion of PCa, whereas co-expression of miR-137 mimics inhibited these behaviors. These observations suggest that miR-137 mimics inhibit development of PCa by antagonizing expression of ANT2. Furthermore, tumorigenic assays in nude mice showed that miR-137 inhibitors abolished the inhibitory effect of ANT2 knockdown on PCa tumor growth. Collectively, our findings suggest that ANT2, a target gene of miR-137, is intimately involved in development of PCa, providing new evidence for the mechanism underlying pathogenesis of PCa as well as new options for targeted therapy.
前列腺癌（PCa）是一种影响男性健康的严重疾病。迄今为止，临床上尚无针对该病症的有效且持久的治疗方案。ANT2在多种激素相关癌症中高表达，但其与前列腺癌的关系及调控机制尚不清楚。在本研究中，我们发现相对于对照样本，ANT2在前列腺癌组织中的表达显著上调。ANT2基因敲低有效抑制了前列腺癌细胞的增殖、迁移和侵袭，而过表达则促进了这些过程。此外，相对于对照组织，前列腺癌组织中miR-137的表达降低。我们在ANT2 mRNA的3'-UTR中鉴定出一个miR-137的调控位点；荧光素酶报告基因检测表明ANT2是miR-137的直接靶基因。用miR-137模拟物和/或编码ANT2的质粒转染细胞表明，ANT2促进前列腺癌的增殖、迁移和侵袭，而共表达miR-137模拟物则抑制这些行为。这些观察结果表明，miR-137模拟物通过拮抗ANT2的表达来抑制前列腺癌的发展。此外，裸鼠致瘤试验表明，miR-137抑制剂消除了ANT2敲低对前列腺癌肿瘤生长的抑制作用。总体而言，我们的研究结果表明，作为miR-137靶基因的ANT2密切参与前列腺癌的发展，为前列腺癌发病机制提供了新的证据以及靶向治疗的新选择。
