# Metastasis-Specific CpG Island DNA Hypermethylation of the Long Non-Coding RNA Gene 00404 in Renal Cell Carcinoma

## TL;DR

The study finds that DNA hypermethylation in the LINC00404 gene is linked to metastasis in kidney cancer, suggesting a role in cancer progression.

## Contribution

This is the first study to identify metastasis-specific DNA hypermethylation in the LINC00404 gene in renal cell carcinoma.

## Key findings

- DNA hypermethylation of LINC00404 is associated with advanced and metastatic renal cell carcinoma.
- Metastatic tissues show more extensive and significant hypermethylation compared to non-metastatic tumors.
- Elevated DNA methylation is observed in most cancer cell line models of LINC00404.

## Abstract

Alterations in long non-coding RNAs (lncRNAs) are known to influence tumor biology in human cancers, including renal cell carcinoma (RCC). Here, DNA hypermethylation of CpG sites within the LINC00404 gene in RCC is associated with advanced and metastatic disease, as well as with RCC metastases. These findings suggest that aberrant methylation of LINC00404 may contribute to the development and progression of RCC.

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 the LINC00404 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. Results: Our analysis revealed that all CpG sites exhibited tumor-specific hypermethylation (all p ≤ 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 that LINC00404 may play a pivotal role in the malignant development and progression of RCC metastasis, as well as in other human cancers.