SNPs in miRNAs and Target Sequences: Role in Cancer and Diabetes

Chhichholiya, Yogita; Suryan, Aman Kumar; Suman, Prabhat; Munshi, Anjana; Singh, Sandeep

doi:10.3389/fgene.2021.793523

Cited by 20 publications

(17 citation statements)

References 230 publications

(290 reference statements)

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“…The UTR variants can alter the binding site of miRNAs, impairing their regulatory capacity; they may also generate a new binding site for other miRNAs, resulting in an imbalance of cellular homeostasis. A limited number of studies have described variants in UTRs in cancer [ 81 , 82 , 83 ], and our findings form the basis for future studies into the biological and functional impact of somatic variants in these regions on penile carcinogenesis.…”

Section: Discussionmentioning

confidence: 66%

Mutational Signature and Integrative Genomic Analysis of Human Papillomavirus-Associated Penile Squamous Cell Carcinomas from Latin American Patients

Canto¹,

Silva

Castelo-Branco

et al. 2022

Cancers

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High-throughput DNA sequencing has allowed for the identification of genomic alterations and their impact on tumor development, progression, and therapeutic responses. In PSCC, for which the incidence has progressively increased worldwide, there are still limited data on the molecular mechanisms involved in the disease pathogenesis. In this study, we characterized the mutational signature of 30 human papillomavirus (HPV)-associated PSCC cases from Latin Americans, using whole-exome sequencing. Copy number variations (CNVs) were also identified and compared to previous array-generated data. Enrichment analyses were performed to reveal disrupted pathways and to identify alterations mapped to HPV integration sites (HPVis) and miRNA–mRNA hybridization regions. Among the most frequently mutated genes were NOTCH1, TERT, TTN, FAT1, TP53, CDKN2A, RYR2, CASP8, FBXW7, HMCN2, and ITGA8. Of note, 92% of these altered genes were localized at HPVis. We also found mutations in ten novel genes (KMT2C, SMARCA4, PTPRB, AJUBA, CR1, KMT2D, NBEA, FAM135B, GTF2I, and CIC), thus increasing our understanding of the potential HPV-disrupted pathways. Therefore, our study reveals innovative targets with potential therapeutic benefits for HPV-associated PSCCs. The CNV analysis by sequencing (CNV-seq) revealed five cancer-associated genes as the most frequent with gains (NOTCH1, MYC, NUMA1, PLAG1, and RAD21), while 30% of the tumors showed SMARCA4 with loss. Additionally, four cancer-associated genes (CARD11, CSMD3, KDR, and TLX3) carried untranslated regions (UTRs) variants, which may impact gene regulation by affecting the miRNAs hybridization regions. Altogether, these data contribute to the characterization of the mutational spectrum and its impact on cellular signaling pathways in PSCC, thus reinforcing the pivotal role of HPV infection in the molecular pathogenesis of these tumors.

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Section: Discussionmentioning

confidence: 66%

Mutational Signature and Integrative Genomic Analysis of Human Papillomavirus-Associated Penile Squamous Cell Carcinomas from Latin American Patients

Canto¹,

Silva

Castelo-Branco

et al. 2022

Cancers

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“…Mounting evidences have shown their important role in the etiology and prognosis of HCC as aberrant expression of miRNAs is involved in proliferation, differentiation and apoptosis of tumor cells [13][14][15] . SNPs in miRNAs may affect individual's susceptibility to cancer by altering mRNA expression of their own or target genes [16][17][18][19][20] . Over-expression of miR-106b was observed in a variety of human malignancies, including colorectal cancer, gastric cancer, and HCC [21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

Impact Of Mir-106b And ATF5 3′UTR Polymorphisms On The Risk Of Hepatocellular Cancer In A Guangxi Population

Liu,

Qiu,

Qiu

et al. 2023

Preprint

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Objectives: Polymorphisms of miRNAs have become a powerful tool for studying disease biology and are used in the prognosis and diagnosis of various diseases, including liver cancer. In this research, we want to evaluate the effect of miR-106b and ATF5 polymorphisms on hepatocellular cancer (HCC). Methods: Three single nucleotide polymorphisms on miR-106b and ATF5 were selected for genotyping by Agena MassARRAY in 813 HCC patients and 896 healthy controls. After analysis using PLINK software, Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to assess the risk of HCC. Results: We evaluated the combined effect of SNP rs2261360, rs1527423 and rs8647 on the risk of HCC and found that the combined 1-3 risk genotypes were significantly associated with the high risk of HCC (OR = 1.52, 95% CI = 1.09‐2.12, P = 0.013) after adjusting for variables such as sex, age, drinking history, smoking history, HBV infection. Further stratification analysis showed that Similar joint effects of these 3 SNPs restricted the risk of HCC in males, non-smoking, non-drinking, and people infected with HBV were more pronounced related to a decreased HCC risk. Conclusions: This study provides evidence that miR-106b rs2261360 decreased the risk of HCC. The miR-106b rs2261360 wild type, rs1527423 mutant, and ATF5 rs8647 wild type may collectively contribute to the risk of HCC.

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“…Approximately 11% of all SNPs are located in the 3′-UTR of genes, potentially disturbing their binding by microRNAs [ 26 , 27 , 28 ]. SNPs located in mature miRNA coding regions or target sites could disturb miRNA-mRNA interactions, altering miRNA-regulated gene expression, which is implicated in various human diseases, including cancer [ 26 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population with PLK1 Variant rs27770A>G

Liao,

Zhang,

Yang

et al. 2023

Cancers

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Hepatocellular carcinoma (HCC) has the highest incidence and mortality in the Asian population, and race is an independent risk factor affecting survival time in liver cancer. Micro RNAs (miRNAs) are remarkably dysregulated in HCC and closely associated with HCC prognosis. Recent studies show that genetic variability between ethnic groups may result in differences in the specificity of HCC miRNA biomarkers. Here, we reveal a high expression level of hsa-miR-100-5p, an HCC prognosis-related miRNA, which improves HCC prognosis in the Asian Population with Polo-like kinase 1 (PLK1) variant rs27770A>G. In this study, we discovered that hsa-miR-100-5p was downregulated in various HCC cell lines. While mimics transient transfection and mouse liver cancer model confirmed the interaction between hsa-miR-100-5p and PLK1, a stratified analysis based on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data suggest both low hsa-miR-100-5p expression level and high PLK1 expression level associated with poor HCC prognosis, especially in the Asian population. According to the 1000 Genomes Project database, the SNP rs27770 located in 3′UTR of PLK1 had a significantly higher G allele frequency in the East Asian population. Bioinformatics analysis suggested that rs27770 A>G affects PLK1 mRNA secondary structure and alters the hsa-miR-100-5p/PLK1 interaction by forming an additional seedless binding site. This racial variation caused PLK1 to be more vulnerable to hsa-miR-100-5p inhibition, resulting in hsa-miR-100-5p being more favorable for HCC prognosis in the Asian population.

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SNPs in miRNAs and Target Sequences: Role in Cancer and Diabetes

Cited by 20 publications

References 230 publications

Mutational Signature and Integrative Genomic Analysis of Human Papillomavirus-Associated Penile Squamous Cell Carcinomas from Latin American Patients

Mutational Signature and Integrative Genomic Analysis of Human Papillomavirus-Associated Penile Squamous Cell Carcinomas from Latin American Patients

Impact Of Mir-106b And ATF5 3′UTR Polymorphisms On The Risk Of Hepatocellular Cancer In A Guangxi Population

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population with PLK1 Variant rs27770A>G

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