LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme

Abstract

This study aimed to reveal the mechanism by which long noncoding RNAs (lncRNAs) modulate hepatocellular carcinoma (HCC) by regulating mRNA via the N6-methyladenosine (m6A) enzyme. The expression and clinical data of 365 HCC patients and 50 healthy control samples were downloaded from the the Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) screened using limma packages from the R. m6A2Target database were used to predict the relationship between m6A enzyme-lncRNA and m6A enzyme-mRNA. The mRNAs in the lncRNA-m6A enzyme-mRNA network were subjected to enrichment analysis. Cox regression analysis was used to screen for RNAs significantly related to HCC prognosis. The expression of differentially expressed RNAs (DERs) was verified using the TCGA dataset and GSE55092. Eighty-five DElncRNAs and 747 DEmRNAs were identified. The mRNAs in the lncRNA-m6A enzyme-mRNA network were primarily involved in mitotic cell division, the p53 signaling pathway, and the cell cycle. Three lncRNAs and 14 mRNAs were significantly associated with HCC prognosis. Furthermore, the expression of 12 DERs differed significantly between patients in the early and advanced stages. LINC00665 was predicted to regulate 11 mRNAs by modulating IGF2BP1, IGF2BP2, and YTHDF1. Thus, this study provides new insights into the roles of lncRNA and m6A enzymes in HCC.

Identification of m6A-Related lncRNA to Predict the Prognosis of Patients with Hepatocellular Carcinoma

“…The overall prognosis for HCC patients is poor, with a 5-year survival rate of less than 5% in underdeveloped areas [ 41 ]. Therefore, prognostic signature which can distinguish high-risk and low-risk patients is essential for determining optimal therapeutic strategies and improving survival outcomes of HCC patients.…”

Emerging role of RNA modification and long noncoding RNA interaction in cancer

“…The lncRNA lnc-H2AFV-1 upregulates the expression of intraflagellar transport (IFT) 80 by regulating METTL3/14 and FTO in head and neck squamous cell carcinoma (HNSCC), thereby promoting cell growth [ 62 ]. LINC00665 can modulate 11 mRNAs by regulating m6A enzymes YTHDF1, IGF2BP1, and IGF2BP2 in hepatocellular carcinoma (HCC) [ 63 ]. Furthermore, it is increasingly clear that m6A and lncRNAs may contribute to the clinical application of cancer therapy [ 64 ].…”