文章：

肾细胞癌中长链非编码RNA基因00404的转移特异性CpG岛DNA高甲基化

Metastasis-Specific CpG Island DNA Hypermethylation of the Long Non-Coding RNA Gene00404in Renal Cell Carcinoma

原文发布日期：30 June 2025

DOI: 10.3390/cancers17132204

类型: Article

开放获取: 是

英文摘要：

Background/Objectives:Alterations in long non-protein-coding RNAs (lncRNAs) are known to influence cellular proliferation, apoptosis, and metastasis in human cancers, including renal cell carcinoma (RCC).Methods:Using pyrosequencing, we analyzed DNA methylation (DNAm) at 23 loci within theLINC00404CpG island across 28 human cancer cell line models, 181 RCC tumor tissues, 154 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples.Results:Our analysis revealed that all CpG sites exhibited tumor-specific hypermethylation (allp≤ 1.4 × 10−5). Moreover, primary RCC tissues with distant metastases (M1) and metastatic tissue samples (Mtx) showed significant hypermethylation compared to RCC without distant metastases (M0). Notably, DNAm in Mtx displayed a significant increase in 22 CpG sites, compared to 12 CpG sites in the M1/M0 comparison, suggesting that DNAm in Mtx differs both qualitatively and quantitatively.Conclusions:Given that elevated levels of DNAm were also observed in the majority of cell line models, our findings suggest thatLINC00404may play a pivotal role in the malignant development and progression of RCC metastasis, as well as in other human cancers.

摘要翻译： 

**背景/目的：** 已知长链非编码RNA（lncRNA）的改变会影响包括肾细胞癌（RCC）在内的人类癌症的细胞增殖、凋亡和转移。 **方法：** 通过焦磷酸测序技术，我们在28个人类癌细胞系模型、181例RCC肿瘤组织、154例配对癌旁正常组织（adNs）以及194例转移组织样本中，分析了LINC00404 CpG岛内23个位点的DNA甲基化（DNAm）状态。 **结果：** 分析显示，所有CpG位点均呈现肿瘤特异性高甲基化（所有p ≤ 1.4 × 10⁻⁵）。此外，与无远处转移的RCC（M0）相比，伴有远处转移的原发性RCC组织（M1）及转移组织样本（Mtx）均表现出显著的高甲基化。值得注意的是，与M1/M0比较中仅12个CpG位点出现显著变化相比，Mtx中的DNAm在22个CpG位点显著升高，表明Mtx中的DNAm在质和量上均存在差异。 **结论：** 鉴于在多数细胞系模型中也观察到DNAm水平升高，我们的研究结果表明，LINC00404可能在RCC转移的恶性发展及进展中，以及其他人类癌症中发挥关键作用。

原文链接：

Metastasis-Specific CpG Island DNA Hypermethylation of the Long Non-Coding RNA Gene00404in Renal Cell Carcinoma