Tung Min-Che, Lin Chia-Yen, Wen Yu-Ching, Chang Lun-Ching, Yang Shun-Fa, Chien Ming-Hsien
Division of Urology, Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
J Cell Mol Med. 2024 Dec;28(23):e70264. doi: 10.1111/jcmm.70264.
Genetic variants of deregulated long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, cancer progression and cancer recurrence. Single-nucleotide polymorphisms (SNPs) of the lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) have been associated with the risk and progression of various cancers; however, their role in prostate cancer (PCa) remains underexplored. In this case-control study, we investigated the associations of CDKN2B-AS1 expression levels and variants with PCa risk and progression. For this, five SNPs of CDKN2B-AS1-rs564398, rs1333048, rs1537373, rs2151280 and rs8181047-were genotyped using a TaqMan allelic discrimination assay; data were collected from 695 patients with PCa and 695 healthy controls. Our findings revealed that, under a dominant model, patients with PCa carrying at least one minor C allele of rs1333048 exhibited an increased risk of developing tumours with high Gleason grades; this risk was particularly high in patients without biochemical recurrence. Data from the Genotype-Tissue Expression database indicated upregulated CDKN2B-AS1 expression in the prostates of individuals carrying the polymorphic C allele of rs1333048. Genotype screening of rs1333048 in PCa cell lines showed that cells with at least one minor C allele had higher CDKN2B-AS1 levels than those with the AA genotype. Furthermore, data from The Cancer Genome Atlas indicated that higher CDKN2B-AS1 levels in PCa tissues were correlated with larger tumour sizes (T3 + T4), more lymph node metastasis (N1), higher Gleason scores and shorter progression-free survival. In conclusion, the polymorphic variants of CDKN2B-AS1 at rs1333048 may modulate CDKN2B-AS1 expression, thus accelerating PCa progression.
长链非编码RNA（lncRNA）失调的基因变异与肿瘤发生、癌症进展和癌症复发有关。细胞周期蛋白依赖性激酶抑制剂2B反义RNA 1（CDKN2B-AS1）的单核苷酸多态性（SNP）与多种癌症的风险和进展相关；然而，它们在前列腺癌（PCa）中的作用仍未得到充分研究。在这项病例对照研究中，我们调查了CDKN2B-AS1表达水平和变异与PCa风险及进展的关联。为此，使用TaqMan等位基因鉴别分析对CDKN2B-AS1的5个SNP（rs564398、rs1333048、rs1537373、rs2151280和rs8181047）进行基因分型；数据收集自695例PCa患者和695例健康对照。我们的研究结果显示，在显性模型下，携带rs1333048至少一个次要C等位基因的PCa患者发生高Gleason分级肿瘤的风险增加；这种风险在无生化复发的患者中尤其高。来自基因型-组织表达数据库的数据表明，携带rs1333048多态性C等位基因的个体前列腺中CDKN2B-AS1表达上调。在PCa细胞系中对rs1333048进行基因分型显示，至少有一个次要C等位基因的细胞比AA基因型的细胞具有更高的CDKN2B-AS1水平。此外，来自癌症基因组图谱的数据表明，PCa组织中较高的CDKN2B-AS1水平与更大的肿瘤大小（T3+T4）、更多的淋巴结转移（N1）、更高的Gleason评分和更短的无进展生存期相关。总之，rs1333048处CDKN2B-AS1的多态性变异可能调节CDKN2B-AS1表达，从而加速PCa进展。
