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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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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...
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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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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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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...
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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
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MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6.

Akiyo Yoshida1,2, Shunsuke Kitajima1,3, Fengkai Li1

  • 1Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.

Oncotarget
|January 19, 2017
PubMed
Summary
This summary is machine-generated.

Retinoblastoma (Rb) protein loss promotes aggressive tumor growth by altering microRNA expression. miR-140 counteracts this effect by downregulating IL-6, offering a potential therapeutic target for cancer.

Keywords:
RBcancercancer stem cellsinterleukin-6mir-140

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The retinoblastoma (Rb) protein is a critical tumor suppressor.
  • Rb pathway inactivation is common in many cancers.
  • Understanding Rb's role in tumor progression is vital for developing new therapies.

Purpose of the Study:

  • To investigate novel activities of the Rb protein during tumor progression using an in vitro cell culture system.
  • To identify microRNAs (miRNAs) associated with Rb status and tumor aggressiveness.
  • To elucidate the regulatory mechanism of miR-140 in Rb-mediated tumor suppression.

Main Methods:

  • Established an in vitro cell culture system using p53-null mouse soft tissue sarcoma cells.
  • Depleted Rb protein to induce spherogenesis and analyzed cell behavior.
  • Utilized miRNA profiling to identify differentially expressed miRNAs.
  • Performed functional studies to assess the role of mmu-miR-140 in regulating spherogenesis and IL-6 expression.
  • Validated findings in a human breast cancer cell line (MCF-7).

Main Results:

  • Rb depletion induced a spherogenic phenotype with increased aggressiveness.
  • Six miRNAs, including mmu-miR-140, showed correlation with Rb status and spherogenic activity.
  • mmu-miR-140 positively regulated by Rb, antagonized Rb depletion effects on spherogenesis.
  • Rb depletion upregulated IL-6, while mmu-miR-140 overexpression downregulated IL-6, targeting its 3'-untranslated region.
  • The RB-miR-140-IL-6 axis was conserved in human breast cancer cells.

Conclusions:

  • Rb protein influences tumor progression partly through regulating specific miRNAs.
  • mmu-miR-140 acts as a tumor suppressor by downregulating IL-6, mediated by Rb.
  • The identified RB-miR-140-IL-6 pathway represents a potential therapeutic target in cancers with RB pathway inactivation.
  • hsa-miR-140 may serve as a therapeutic tool to disrupt the link between tumor suppressor inactivation and pro-inflammatory cytokine response.