The dicey role of Dicer: implications for RNAi therapy

William M Merritt1, Menashe Bar-Eli, Anil K Sood

  • 1Department of Gynecologic Oncology, M.D. Anderson Cancer Center, Houston, Texas.

Cancer Research
|February 25, 2010
PubMed

Insights

Decreased expression of RNA interference (RNAi) enzymes Dicer and Drosha correlates with poor outcomes in ovarian cancer. This suggests RNAi machinery is vital for cancer biology and developing RNAi therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • RNA interference (RNAi) plays a dynamic role in cancer biology, influencing tumorigenesis and therapeutic strategies.
  • Recent findings indicate a link between reduced expression of key RNAi enzymes and adverse clinical outcomes in epithelial ovarian cancers.

Purpose of the Study:

  • To investigate the significance of RNA interference (RNAi) machinery expression in epithelial ovarian cancer.
  • To explore the functional relevance of Dicer enzyme in RNAi-mediated gene silencing within cancer cells.

Main Methods:

  • Analysis of Dicer and Drosha enzyme expression levels in epithelial ovarian cancer patient samples.
  • Functional assessment of RNAi efficacy based on Dicer-dependent and Dicer-independent silencing fragments.

Main Results:

  • Decreased expression of Dicer and Drosha was significantly associated with poor clinical outcomes in ovarian cancer patients.
  • Targeted gene silencing was less effective when RNAi fragments relied on Dicer function, highlighting its functional importance.

Conclusions:

  • The expression levels of RNAi machinery, including Dicer and Drosha, appear to impact key pathways in cancer biology and tumorigenesis.
  • Understanding alterations in RNAi functional machinery is crucial for advancing novel RNAi-based therapeutic strategies in cancer treatment.

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
Types of RNA01:20

Types of RNA

Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...