Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 400042 Chongqing, China.
Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, 400016 Chongqing, China.
Genomics. 2023 Mar;115(2):110599. doi: 10.1016/j.ygeno.2023.110599. Epub 2023 Mar 6.
Prostate cancer (PCa) is a common malignant cancer in elderly males in Western countries. Whole-genome sequencing confirmed that long non-coding RNAs (lncRNAs) are frequently altered in castration-resistant prostate cancer (CRPC) and promote drug resistance to cancer therapy. Therefore, elucidating the prospective role of lncRNAs in PCa oncogenesis and progression is of remarkable clinical significance. In this study, gene expression in prostate tissues was determined using RNA-sequencing datasets, and the gene diagnostic and prognostic values of CRPC were analyzed using bioinformatics. Further, the expression levels and clinical significance of MAGI2 Antisense RNA 3 (MAGI2-AS3) in PCa clinical specimens were evaluated. The tumor-suppressive activity of MAGI2-AS3 was functionally explored in PCa cell lines and animal xenograft models. MAGI2-AS3 was found to be aberrantly decreased in CRPC and was negatively correlated with Gleason score and lymph node status. Notably, low MAGI2-AS3 expression positively correlated with poorer survival in patients with PCa. The overexpression of MAGI2-AS3 significantly inhibited the proliferation and migration of PCa in vitro and in vivo. Mechanistically, MAGI2-AS3 could play a tumor suppressor function in CRPC through a novel miR-106a-5p/RAB31 regulatory network and could be a target for future cancer therapy.
前列腺癌(PCa)是西方国家老年男性中常见的恶性肿瘤。全基因组测序证实,长链非编码 RNA(lncRNA)在去势抵抗性前列腺癌(CRPC)中经常发生改变,并促进癌症治疗的耐药性。因此,阐明 lncRNA 在 PCa 发生和发展中的潜在作用具有重要的临床意义。在这项研究中,使用 RNA-seq 数据集确定了前列腺组织中的基因表达,并使用生物信息学分析了 CRPC 的基因诊断和预后价值。进一步评估了 MAGI2 Antisense RNA 3(MAGI2-AS3)在 PCa 临床标本中的表达水平和临床意义。在 PCa 细胞系和动物异种移植模型中研究了 MAGI2-AS3 的肿瘤抑制活性。结果发现,MAGI2-AS3 在 CRPC 中异常下调,与 Gleason 评分和淋巴结状态呈负相关。值得注意的是,MAGI2-AS3 低表达与 PCa 患者的生存预后较差呈正相关。MAGI2-AS3 的过表达显著抑制了 PCa 在体外和体内的增殖和迁移。机制上,MAGI2-AS3 可以通过新型 miR-106a-5p/RAB31 调控网络在 CRPC 中发挥肿瘤抑制作用,可能成为未来癌症治疗的靶点。