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

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). Using pyrosequencing, we analyzed DNA methylation (DNAm) at 23 loci within the CpG island across 28 human cancer cell line models, 181 RCC tumor tissues, 154 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples. Our analysis revealed that all CpG sites exhibited tumor-specific hypermethylation (all ≤ 1.4 × 10). 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. Given that elevated levels of DNAm were also observed in the majority of cell line models, our findings suggest that may play a pivotal role in the malignant development and progression of RCC metastasis, as well as in other human cancers.