Activation of an oncogenic microRNA cistron by provirus integration

Clifford L Wang1, Bruce B Wang, Gábor Bartha

  • 1Department of Microbiology and Immunology, University of California-San Francisco, San Francisco, CA 94143, USA. cliff.wang@stanford.edu

Insights

Retroviral mutagenesis can activate oncogenic microRNAs (miRNAs) by integrating near miRNA genes, leading to tumor development. This study highlights retroviral mutagenesis as a powerful method for discovering new oncogenic miRNAs.

Area of Science:

  • Oncology
  • Virology
  • Genetics

Background:

  • Retroviruses are known to induce tumors by integrating near host protooncogenes or tumor suppressor genes.
  • MicroRNAs (miRNAs) play crucial roles in gene regulation and can function as oncogenes or tumor suppressors.

Purpose of the Study:

  • To investigate whether retroviral mutagenesis can lead to the activation of oncogenic microRNAs (miRNAs).
  • To explore the potential of retroviral mutagenesis as a tool for discovering novel oncogenic miRNAs.

Main Methods:

  • Infection of over 2,500 mice with the SL3-3 murine leukemia virus.
  • Analysis of tumor genomes to identify provirus integration sites near miRNA genes.
  • Quantitative real-time PCR to measure miRNA expression levels in tumors.

Main Results:

  • Provirus integrations were found near or within the mir-17-92 microRNA (miRNA) cistron in 22 out of the resulting tumors.
  • Quantitative real-time PCR confirmed increased expression of this miRNA in the tumors.
  • This indicates that retroviral infection can induce the expression of oncogenic miRNAs.

Conclusions:

  • Retroviral mutagenesis can activate oncogenic miRNAs, contributing to tumor formation.
  • Retroviral mutagenesis serves as an effective strategy for the discovery of novel oncogenic miRNAs.

Related Concept Videos

Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

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).
Somatic cells are...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
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...