A New Understanding of Long Non-Coding RNA in Hepatocellular Carcinoma—From m6A Modification to Blood Biomarkers

Abstract

With recent advancements in biological research, long non-coding RNAs (lncRNAs) with lengths exceeding 200 nucleotides have emerged as pivotal regulators of gene expression and cellular phenotypic modulation. Despite initial skepticism due to their low sequence conservation and expression levels, their significance in various biological processes has become increasingly apparent. We provided an overview of lncRNAs and discussed their defining features and modes of operation. We then explored their crucial function in the hepatocarcinogenesis process, elucidating their complex involvement in hepatocellular carcinoma (HCC). The influential role of lncRNAs within the HCC tumor microenvironment is emphasized, illustrating their potential as key modulators of disease dynamics. We also investigated the significant influence of N6-methyladenosine (m6A) modification on lncRNA function in HCC, enhancing our understanding of both their roles and their upstream regulators. Additionally, the potential of lncRNAs as promising biomarkers was discussed in liver cancer diagnosis, suggesting a novel avenue for future research and clinical application. Finally, our work underscored the dual potential of lncRNAs as both contributors to HCC pathogenesis and innovative tools for its diagnosis. Existing challenges and prospective trajectories in lncRNA research are also discussed, emphasizing their potential in advancing liver cancer research.

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

“…In addition, for m5C methylase, azacitidine, and decitabine are cytidine analogs that inhibit any m5C methylase and have been approved for clinical use in hematological malignancies [ 205 ]. Abnormally expressed m6A-related lncRNAs were recently discovered in the peripheral blood of HCC patients, suggesting that m6A-modified lncRNAs have good clinical application prospects as biomarkers [ 206 ]. Over the past few years, the development of lncRNA therapeutics have been witnessed [ 207 ], and the field of RNA-modifying proteins as drug targets is expanding [ 208 ].…”

Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention

“…One notable mechanism employed by NATs to enhance protein stability involves the prevention of proteasomal degradation [ 51 ]. An illustrative case is demonstrated by the antisense transcript KDM4A-AS1, which forms a binding partnership with the androgen receptor (AR) protein [ 52 ]. This connection facilitates the stabilization of the Androgen Receptor (AR) by facilitating the process of deubiquitination of AR via the formation of the USP14 (ubiquitin-specific protease 14)-AR complex.…”

New understandings of the genetic regulatory relationship between non-coding RNAs and m6A modification

“…With the gradual increase in the importance of m 6 A modification in the medical community, abnormally expressed m 6 A-related non-coding RNAs have recently been identified in peripheral bloodstreams of patients who suffer from cancers, which tremendously improves the convenience and utility of m 6 A-modified non-coding RNAs as biomarkers with good prospects for clinical application ( Eun et al, 2023 ). In addition, cancer has inappropriate expression of m 6 A-related proteins, which accordingly affects the m 6 A level of ncRNAs.…”