Abstract
miRNAs are fascinating molecular players for gene regulation as individual miRNA can control multiple targets and a single target can be regulated by multiple miRNAs. Loss of miRNA regulated gene expression is often reported to be implicated in various human diseases like diabetes and cancer. Recently, geneticists across the world started reporting single nucleotide polymorphism (SNPs) in seed sequences of miRNAs. Similarly, SNPs are also reported in various target sequences of these miRNAs. Both the scenarios lead to dysregulated gene expression which may result in the progression of diseases. In the present paper, we explore SNPs in various miRNAs and their target sequences reported in various human cancers as well as diabetes. Similarly, we also present evidence of these mutations in various other human diseases.
Highlights
MicroRNAs are endogenous single stranded, non-coding, 20–22 nucleotides long molecules that are processed from pre-miRNA. miRNAs have been demonstrated to be tremendously versatile in their function. miRNAs have significant roles in the nucleus as well as cytoplasm in terms of controlling gene expression
In vitro studies on HUVEC cell lines showed that the C allele expression was five times higher than T allele suggesting that C>T transition reduces its level which results in the overexpression of its targets; GSTM1 and Trib3 (Tribbles pseudokinase3)
SIRT2 levels have been discovered to be low in various human malignancies, and SIRT2-deficient animals have been reported to develop tumors as they age (Hiratsuka et al, 2003; Kim et al, 2011; Li et al, 2013b). miR-615-5p, which has the highest binding energy change caused by rs45592833, has been found to be deregulated in cancer cell lines, patients with aging-related conditions such as Huntington’s and cardiovascular diseases, and in the muscles of old mice, implying that miR-615-5p downstream targets may be involved in signaling pathways that are important in the aging process (Hulf et al, 2011; Sondermeijer et al, 2011; Hoss et al, 2014; Gao et al, 2015b)
Summary
MicroRNAs (miRNAs) are endogenous single stranded, non-coding, 20–22 nucleotides long molecules that are processed from pre-miRNA. miRNAs have been demonstrated to be tremendously versatile in their function. miRNAs have significant roles in the nucleus as well as cytoplasm in terms of controlling gene expression. The SNPs in the 3′UTRs of gene/mRNA can modulate miRNA-mRNA interactions, protein-mRNA interactions, polyadenylation, all of which might have a serious impact on translation efficiency and mRNA stability (Malhotra et al, 2019a) This in turn might result in the development of various diseases including neurodevelopment disorders, cardiovascular diseases, cancer, autoimmune diseases, and many more (Bruno et al, 2012; Moszyńska et al, 2017). The current review has been compiled with an aim to evaluate the role of genetic variation in the seed sequence of the miRNA and the 3′UTR of their specific target genes in association with the development of the two most common prevalent diseases—cancer and diabetes. SNPS IN THE SEED SEQUENCE OF MIRNA AND THE 39UTR OF SPECIFIC TARGET GENE IN CANCER.
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