Department of Urology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
DNA Cell Biol. 2023 Sep;42(9):563-577. doi: 10.1089/dna.2023.0089. Epub 2023 Aug 4.
N-cadherin (cadherin-2 [CDH2]) is widely known as the promoter of prostate cancer (PCa) invasion and castration resistance. However, the biological mechanism of N-cadherin in PCa progression is unclear. In this study, we overexpressed N-cadherin in LNCaP cells and downregulated N-cadherin in PC3 cells by lentiviral transduction. Then, differentially expressed genes (DEGs) and dysregulated biological functions were investigated through RNA sequencing (RNA-seq) analyses. We found 13 long noncoding RNA (lncRNA) transcripts, 72 messenger RNA (mRNA) transcripts, and 3 integrated genes were dysregulated by N-cadherin. In the disease enrichment, bone cancer, and neurodegenerative and nervous system diseases were associated with N-cadherin in the circular RNA (circRNA; PC3 versus [vs.,/] LNCaP [PC3/LNCaP] comparison) and DEG analysis (LNCaP_oe_CDH2 vs. LNCaP_oe_NC [LNCaP_oe_CDH2/NC] comparison). Epigenetic reprogramming, such as nucleic acid binding, and chromatin and histone modifications, was enriched in Gene Ontology (GO) analysis (DEGs in LNCaP_oe_CDH2/NC and PC3_sh_NC/CDH2, and host genes of circRNA in PC3/LNCaP). Transcriptional misregulation in cancer, post-translational protein modification, gene expression, and generic transcription pathways were dysregulated in the pathway enrichment analysis (host genes of circRNA in PC3/LNCaP, and DEGs in LNCaP_oe_CDH2/NC and PC3_sh_NC/CDH2). Verifying DEGs through TCGA-PRAD dataset revealed six oncogenes (ARHGEF1, GRAMD1A, GTF2H4, MAPK8IP3, POLD1, and PTBP1) that were commonly upregulated by N-cadherin and in advanced PCa stages. In summary, we identified several oncogenes and biological functions associated with N-cadherin expression in PCa cells. N-cadherin may trigger epigenetic reprogramming in PCa cells to promote tumor progression.
N-钙黏蛋白（钙黏蛋白-2 [CDH2]）被广泛认为是促进前列腺癌（PCa）侵袭和去势抵抗的因素。然而，N-钙黏蛋白在 PCa 进展中的生物学机制尚不清楚。在本研究中，我们通过慢病毒转导过表达 LNCaP 细胞中的 N-钙黏蛋白，下调 PC3 细胞中的 N-钙黏蛋白。然后，通过 RNA 测序（RNA-seq）分析研究差异表达基因（DEG）和失调的生物学功能。我们发现 13 个长链非编码 RNA（lncRNA）转录本、72 个信使 RNA（mRNA）转录本和 3 个整合基因受 N-钙黏蛋白调控。在疾病富集分析中，骨癌、神经退行性疾病和神经系统疾病与环状 RNA（circRNA；PC3 与 LNCaP 的比较[PC3/LNCaP]）和 DEG 分析（LNCaP_oe_CDH2 与 LNCaP_oe_NC 的比较[LNCaP_oe_CDH2/NC]）中的 N-钙黏蛋白相关。基因本体论（GO）分析（LNCaP_oe_CDH2/NC 和 PC3_sh_NC/CDH2 中的 DEG 和 circRNA 的宿主基因）中富集了表观遗传重编程，如核酸结合、染色质和组蛋白修饰。通路富集分析（circRNA 的宿主基因在 PC3/LNCaP 中，DEG 在 LNCaP_oe_CDH2/NC 和 PC3_sh_NC/CDH2 中）中失调了转录失调、癌症的翻译后蛋白质修饰、基因表达和通用转录途径。通过 TCGA-PRAD 数据集验证 DEG 显示，六个癌基因（ARHGEF1、GRAMD1A、GTF2H4、MAPK8IP3、POLD1 和 PTBP1）被 N-钙黏蛋白共同上调，并在 PCa 的晚期阶段上调。总之，我们鉴定了与 PCa 细胞中 N-钙黏蛋白表达相关的几个癌基因和生物学功能。N-钙黏蛋白可能触发 PCa 细胞中的表观遗传重编程，以促进肿瘤进展。
