Epitranscriptomic Signatures in lncRNAs and Their Possible Roles in Cancer

Abstract

In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs are post-transcriptional regulators of gene expression, but RNA modifications occurring in lncRNAs generate an additional layer of gene expression control. Chemical modifications that have been reported in correlation with lncRNAs include m6A, m5C and pseudouridylation. Up to date, several chemically modified long non-coding transcripts have been identified and associated with different pathologies, including cancers. This review presents the current level of knowledge on the most studied cancer-related lncRNAs, such as the metastasis associated lung adenocarcinoma transcript 1 (MALAT1), the Hox transcript antisense intergenic RNA (HOTAIR), or the X-inactive specific transcript (XIST), as well as more recently discovered forms, and their potential roles in different types of cancer. Understanding how these RNA modifications occur, and the correlation between lncRNA changes in structure and function, may open up new therapeutic possibilities in cancer.

RNA N6-Methyladenosine Modifications and the Immune Response

“…Furthermore, the METTL3-miR-25-3p-PHLPP2-AKT pathway is associated with pancreatic transformation [32], and m 6 A modifications of AGO2 mRNA contribute to cellular ageing by regulating global miRNA synthesis [33]. It has also been reported that YTHDC1 recognizes m 6 A marks in mESCs and is essential for X-inactive specific transcript (XIST) activity [34]. Recently, it has also been found that enhancer RNAs (eRNAs), noncoding transcripts produced from enhancer regions that act as regulators of transcription, are highly m 6 A modified [35].…”

miRNAs in the Diagnosis and Prognosis of Skin Cancer

“…Long ncRNAs (lncRNAs) have recently been recognized as important regulators of transcriptional, post-transcriptional, and translational processes. lncRNAs are non-coding RNAs (200 nt and 100 kb) with multiple functions as chromatin regulators, ribonucleoprotein scaffolds, regulators of transcription factors, and matrix for other post-transcriptional molecules such as miRNAs (Dinescu et al, 2019).…”

The Function of lncRNAs as Epigenetic Regulators

“…Its high expression has been associated with gastric cancer, melanoma, breast cancer tumour and metastatic progression. MALAT1 also functions in key spots of cancer development process, since it regulates transcription of oncogenic targets and regulates itself interacting with transcription factors [26]. This lncRNA can mediate transcription factors binding to target gene promoters or can act as a sponge to sequester miRNAs, controlling miRNA suppressor effects on oncogenic targets.…”