Transcriptomic analysis reveals heart failure-related lncRNA LINC00670 as a regulator of colon cancer mesenchymal...

Recent evidence suggests that cardiovascular diseases and cancer are linked through circulating factors, mainly proteins with oncogenic properties found in heart failure (HF) patients. However, the role of long non-coding RNAs (lncRNAs) as potential factors in cancer progression associated with HF remains unknown. This study aims to determine the role of HF-related lncRNAs in cancer progression. Using public RNA-sequencing datasets from the left ventricle and whole blood of HF patients, as well as colon cancer tumors, we identified HF-related lncRNAs with predicted competing endogenous RNA (ceRNA) interactions. These were integrated with co-expression analysis and upregulated colon cancer protein-coding genes to construct an HF-related regulatory network associated with colon cancer and epithelial-mesenchymal transition (EMT)-associated genes. LINC00670-overexpressing DLD-1 colon cancer cells showed increased migration and expression of Vimentin, along with N-cadherin, ZEB1, ESRP1, and E-cadherin transcript levels. Long-read nanopore sequencing of LINC00670-overexpressing DLD-1 cells revealed positively correlated genes, including type I interferon signaling pathway genes (STAT1 and SLC7A11) and epithelial-mesenchymal transition (EMT)-associated migratory genes (DDIT4 and PABPC1), as genes associated with the response to HF-related LINC00670 overexpression. Our findings reveal LINC00670 as an HF-related lncRNA that promotes partial EMT-transcriptional changes associated with type I interferon-associated genes, suggesting that LINC00670 plays a key role in inducing mesenchymal traits in the cardio-oncological context.