How miRNA Structure of Animals Influences Their Biogenesis

Vorozheykin, P. S.; Titov, I. I.

doi:10.1134/s1022795420010135

Cited by 3 publications

(3 citation statements)

References 119 publications

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“…With 33 identified mutations, hsa-miR-519e is overmutated in Pan-Cancer and two female-specific cancers, OV (16) and BRCA (6). The majority of the mutations are located in two subsequent hotspot positions, i.e., the 12th and 13th nucleotides (chr19:53679964G>A/T [+] and chr19:53679965G>A[+]) of the miR-519e-5p (passenger) strand (Fig.…”

Section: Hsa-mir-519ementioning

confidence: 99%

“…Considering subsequent steps of miRNA biogenesis and the mechanism of miRNA posttranscriptional gene regulation, mutations may be expected to affect different attributes of miRNA genes. In addition to the most obvious consequences of mutations in seed sequences that affect the pivotal function of miRNAs, i.e., the ability to recognize and downregulate their specific targets, mutations in any part of the miRNA precursor may affect the effectiveness or precision of miRNA biogenesis by altering/destabilizing the hairpin structure of the miRNA precursor, by altering DROSHA or DICER1 cleavage sites, or by altering protein-interacting or other regulatory sequences/structure motifs [16] , [17] , [18] , [19] . Additionally, mutations destabilizing one of the miRNA duplex ends may alter 5p/3p miRNA preference.…”

Section: Introductionmentioning

confidence: 99%

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Pan-cancer analysis of somatic mutations in miRNA genes

et al. 2020

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Background miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Methods Here, based on the analysis of large genomic datasets, mostly the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we undertook an analysis of somatic mutations in miRNA genes. Findings We identified and characterized over 10,000 somatic mutations and showed that some of the miRNA genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Interpretation Our study is the first comprehensive Pan-Cancer study of cancer somatic mutations in miRNA genes. It may help to understand the consequences of mutations in miRNA genes and the identification of miRNA functional mutations. The results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancer-driver miRNA genes. Funding This work was supported by research grants from the Polish National Science Centre 2016/22/A/NZ2/00184 and 2015/17/N/NZ3/03629.

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Section: Hsa-mir-519ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pan-cancer analysis of somatic mutations in miRNA genes

et al. 2020

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“…With 33 identified mutations, hsa-miR-519e is overmutated in Pan-Cancer and two femalespecific cancers, OV (16) and BRCA (6). The majority of the mutations are located in two subsequent hotspot positions, i.e., the 12th and 13th nucleotides (chr19:53679964G>A/T[+]…”

Section: Hsa-mir-519ementioning

confidence: 99%

Pan-Cancer analysis of somatic mutations in miRNA genes

Urbanek-Trzeciak

Galka-Marciniak

Nawrocka

et al. 2020

Preprint

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175)miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Here, based on analysis of the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we identified and characterized over 10,000 somatic mutations in miRNA genes and showed that some of the genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Our results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancerdriver miRNA genes. The results published here are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This work was supported by research grants from the Polish National Science Centre [2016/22/A/NZ2/00184 (to P.K.) and 2015/17/N/NZ3/03629 (to M.O.U-T.)] Authors contributions MUTparticipated in conceiving the study, wrote all the scripts, performed most of the computational and statistical analyses, drafted the manuscript, prepared figures, tables, and supplementary materials; PGMparticipated in conceiving the study, discussed the study on all steps of analyses, participated in manuscript preparation, performed some analyses (3D structures); PNdiscussed the analyses on all steps of the study, performed some analyses, participated in manuscript preparation; EKperformed the sequencing experiments, critically read and corrected manuscript; SSperformed the sequencing experiments, critically read and corrected manuscript; MGprovided samples for the hsa-miR-1324 and hsa-miR-142 sequencing validation experiments, advised on hematological neoplasms and head and neck cancer, critically read and corrected manuscript; PKreceived financing, participated in conceiving the study, supervised and coordinated the study, drafted the manuscript (with MUT).

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