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Related Concept Videos

MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
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Somatic mutation effects diffused over microRNA dysregulation.

Hui Yu1, Limin Jiang1, Chung-I Li2

  • 1Department of Public Health, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, U.S.A.

Bioinformatics (Oxford, England)
|August 25, 2023
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Summary
This summary is machine-generated.

Somatic mutations impact microRNAs (miRNAs), influencing cellular processes and disease prognosis. A new statistical framework rigorously assesses mutation effects on miRNAs, identifying significant impacts and prognostic value in pan-cancer analysis.

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Area of Science:

  • Genomics
  • Transcriptomics
  • Cancer Biology

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression and play roles in disease.
  • Somatic mutations can impact miRNA regulation, influencing cellular processes and disease outcomes.
  • Previous studies often lacked robust statistical methods to account for biases like unequal sample sizes and class imbalance when correlating mutations with gene expression.

Purpose of the Study:

  • To develop and apply a rigorous statistical framework for assessing the impact of somatic mutations on microRNAs.
  • To identify genes with mutation impacts on miRNAs that also possess prognostic value in cancer.

Main Methods:

  • Developed a statistical framework using permutation-based null distribution to assess mutation impact on miRNAs.
  • Applied the framework to a pan-cancer dataset.
  • Incorporated advanced features like miRNA isoform analysis, aggregative prognostic analysis, and detailed annotations.

Main Results:

  • Identified 9008 protein-coding genes with statistically significant mutation impacts on miRNAs.
  • Found that collective miRNA expression for 83 genes showed significant prognostic power across nine cancer types.
  • Demonstrated prognostic value of miRNA expression linked to specific gene mutations in lower-grade glioma.

Conclusions:

  • The developed statistical framework effectively identifies mutation impacts on miRNAs with prognostic significance.
  • This approach provides a robust method for analyzing the complex interplay between somatic mutations, miRNA regulation, and cancer prognosis.
  • The findings highlight specific genes and their associated miRNA expression profiles as potential biomarkers for cancer prognosis.