Analysis of microRNA-target interactions across diverse cancer types

Anders Jacobsen1, Joachim Silber, Girish Harinath

  • 1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Insights

This study reveals how microRNAs (miRNAs) impact tumor biology across many cancers. It identifies key miRNA-target interactions and their regulation, offering insights into cancer development.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • The role of individual microRNAs (miRNAs) in regulating shared tumor biology processes across diverse cancer types remains largely unknown.
  • Understanding these regulatory networks is crucial for advancing cancer research and therapy.

Purpose of the Study:

  • To systematically analyze miRNA and messenger RNA (mRNA) expression across multiple human cancer types.
  • To infer recurrent cancer-associated miRNA-target relationships and identify novel regulatory interactions.
  • To provide a resource for exploring and prioritizing miRNA-target interactions in tumorigenesis.

Main Methods:

  • Utilized molecular profiles from over 3,000 tumors across 11 human cancer types from The Cancer Genome Atlas (TCGA).
  • Performed systematic analysis of miRNA and mRNA expression to infer miRNA-target relationships.
  • Validated inferred relationships against sequence-based predictions and experimental data.

Main Results:

  • Identified recurrent miRNA-target relationships consistent with existing knowledge and predictions.
  • Found that miRNAs with recurrent targets are frequently regulated by genetic and epigenetic alterations in cancer.
  • Discovered new examples of miRNAs coordinating cancer pathways, such as the miR-29 family regulating DNA demethylation (TET1, TDG).

Conclusions:

  • Established a framework for understanding miRNA regulation in pan-cancer tumor biology.
  • Highlighted the significance of genetic and epigenetic alterations in modulating miRNA activity in cancer.
  • Developed an online resource (http://cancerminer.org) to facilitate the study of miRNA-target interactions in cancer.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

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...
MicroRNAs01:22

MicroRNAs

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 ends...
MicroRNAs01:22

MicroRNAs

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 ends...
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...