lncRNAs Participate in Epigenetic Regulation in Brest Cancer
lncRNAs Participate in Epigenetic Regulation in Brest Cancer
zahra mollaei,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: The most frequent malignancy in women and the primary cause of cancer-related deaths globally is breast cancer (BC). Although there have been substantial improvements in clinical therapy, mortality has continued to rise due to the prevalence of breast cancer. Originally, it was believed that long non-coding RNAs (lncRNAs) were just the genome's background noise of transcripts and had no biological purpose. The purpose of lncRNAs has recently come under increased scrutiny. By controlling gene transcription and post-transcriptional processing, studies increasingly demonstrate that lncRNAs have a role in a variety of cellular physiological processes, including proliferation, differentiation, migration, and death. This research looked into how lncRNAs regulate epigenetic changes in breast cancer.
Methods: This review study has been written from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Epigenetic regulation does not alter the DNA sequence to cause heritable changes in gene expression, including DNA methylation, histone modification, genome imprinting, and random chromosome inactivation. Some important functions of lncRNAs are related to the epigenetic control of specific target genes For example, lncRNAs basal-like breast cancer-associated transcript (BLAT1), BCLIN25, and H91 can regulate DNA methylation to participate in tumorigenesis.9) Han found that BLAT1 expression is regulated at the epigenetic level by decreasing DNA methylation of CpG islands in the promoter. Patients with BLAT1-hypomethylated tumors have lower overall survival (OS). The increased BLAT1 expression with hypomethylation at CpG sites may contribute to the aggressive phenotype of breast cancer.57 BCLIN25 increases ERBB2 expression by enhancing CpG methylation of the miR-125b promoter, leading to the downregulation of miR-125b and promoting the occurrence of breast cancer. Also, the lncRNA 91H of the H19/IGF2 locus is transcribed in the H19 antisense orientation. In breast cancer, 91H lncRNA prevents DNA methylation of the maternal allele at the H19/IGF2 locus, thereby increasing the aggressive phenotype of breast cancer cells. In addition, lncRNA also inhibits gene transcription by recruiting histone modification or chromatin remodelling proteins.4 lncRNA HOX transcript antisense RNA (HOTAIR) plays a critical role in chromatin dynamics through the interaction with histone modifiers resulting in transcriptional gene silencing.59 HOTAIR is participated in the silencing of miR-205 by breaking the balance of histone modification between histone H3 at lysine 4 methylation (H3K4me3) and H3K27me3 on the miR-205 promoter to regulate cyclin J (CCNJ) expression.
Conclusion: Breast tumour formation, diagnosis, and treatment, as well as patient prognosis, are all significantly influenced by lncRNAs. A few lncRNAs have currently had their function mechanisms thoroughly examined in exploratory study. Most lncRNAs' underlying functional mechanisms in breast cancer are still poorly understood, though. The secondary structure of lncRNAs is more complex than that of mRNA, and it has been acknowledged that lncRNA expression is more strictly regulated than mRNA. A small portion of lncRNAs expresses polypeptide products, much like mRNA does. As a result, lncRNA function mechanisms are extremely complex. Since the number of lncRNA genes exceeds protein-coding genes, lncRNAs are more stable than mRNA, so they are more suitable. All in all, lncRNAs open a new door for clinical diagnosis and treatment of breast cancer.