Sun Guangyu, Ma Shenfei, Zheng Zhiwen, Wang Xiaohua, Chen Shuaiqi, Chang Taihao, Liang Zhengxin, Jiang Yuchen, Xu Shengxian, Liu Ranlu
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Front Oncol. 2022 Aug 1;12:965571. doi: 10.3389/fonc.2022.965571. eCollection 2022.
Prostate cancer is the most common tumor in men worldwide, seriously threatening the health of older men, and 5-methylcytosine (m5C) RNA modification has been shown to have a significant impact on the development and progression of various tumors. However, as the most critical methyltransferase for m5c RNA modification, the role of the NSUN members (NSUN1-7) in prostate cancer is unclear.
We obtained sequencing data of genes and related clinical data of prostate cancer from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database and analyzed the correlation between NSUN members' expression and prognosis. we found that NSUN2 was closely implicated in the prognosis of prostate cancer, then verified the expression of NSUN2 in clinical samples, and obtained the correlation between NSUN2 and immune cell infiltration through CIBERSORT algorithm and ESTIMATE method. The relationship between NSUN2 copy number variation and immune cell infiltration was further analyzed in the TIMER database and identified signaling pathways associated with NSUN2 expression by GO, KEGG, and GSEA analysis. Finally, we verified the expression of NSUN2 in prostate cancer cell lines and confirmed the role of NSUN2 on the biological behavior of prostate cancer cells by proliferation and migration-related assays.
NOP2 and NSUN2 were upregulated in prostate tumor tissues. NSUN2 expression is closely associated with tumor prognosis. NSUN2 high expression implies poor clinical features, and the NSUN family is significantly associated with tumor stromal score and immune score. Besides, NSUN2 is associated with a variety of immune infiltrating cells (B cells memory, T cells CD4 memory resting, T cells CD4 memory activated, NK cells resting, and so on). High NSUN2 expression lowers the sensitivity of many chemotherapy drugs, such as docetaxel, doxorubicin, fluorouracil, cisplatin, and etoposide. In prostate cancer, the most common type of mutation in NSUN2 is amplification, and NSUN2 copy number variation is closely associated with NSUN2 expression and immune cell infiltration. GSEA analysis showed that the related genes were mainly enriched in ubiquitin-mediated protein hydrolysis, cell cycle, RNA degradation, endometrial cancer, prostate cancer, p53 signaling pathway, and NSUN2 potentiated the proliferation and migration of prostate cancer cells.
NSUN2 is highly expressed in prostate cancer, which contributes to the progression of prostate cancer, and is closely implicated in immune cell infiltration and chemotherapy drugs. NSUN2 is expected to be a prospective marker and a new treatment target for prostate cancer.
前列腺癌是全球男性中最常见的肿瘤，严重威胁老年男性的健康，并且5-甲基胞嘧啶（m5C）RNA修饰已被证明对各种肿瘤的发生和发展有重大影响。然而，作为m5C RNA修饰最关键的甲基转移酶，NSUN成员（NSUN1-7）在前列腺癌中的作用尚不清楚。
我们从癌症基因组图谱（TCGA）数据库和基因表达综合数据库（GEO）获取了前列腺癌的基因测序数据及相关临床数据，并分析了NSUN成员的表达与预后之间的相关性。我们发现NSUN2与前列腺癌的预后密切相关，随后在临床样本中验证了NSUN2的表达，并通过CIBERSORT算法和ESTIMATE方法获得了NSUN2与免疫细胞浸润之间的相关性。在TIMER数据库中进一步分析了NSUN2拷贝数变异与免疫细胞浸润的关系，并通过GO、KEGG和GSEA分析确定了与NSUN2表达相关的信号通路。最后，我们在前列腺癌细胞系中验证了NSUN2的表达，并通过增殖和迁移相关实验证实了NSUN2对前列腺癌细胞生物学行为的作用。
NOP2和NSUN2在前列腺肿瘤组织中上调。NSUN2表达与肿瘤预后密切相关。NSUN2高表达意味着临床特征较差，并且NSUN家族与肿瘤基质评分和免疫评分显著相关。此外，NSUN2与多种免疫浸润细胞（记忆B细胞、静息CD4记忆T细胞、活化CD4记忆T细胞、静息NK细胞等）相关。NSUN2高表达降低了许多化疗药物（如多西他赛、阿霉素、氟尿嘧啶、顺铂和依托泊苷）的敏感性。在前列腺癌中，NSUN2最常见的突变类型是扩增，并且NSUN2拷贝数变异与NSUN2表达和免疫细胞浸润密切相关。GSEA分析表明相关基因主要富集在泛素介导的蛋白质水解、细胞周期、RNA降解、子宫内膜癌、前列腺癌、p53信号通路中，并且NSUN2增强了前列腺癌细胞的增殖和迁移。
NSUN2在前列腺癌中高表达，这促进了前列腺癌的进展，并且与免疫细胞浸润和化疗药物密切相关。NSUN2有望成为前列腺癌的一个有前景的标志物和新的治疗靶点。
