MicroRNA-433 inhibits migration and invasion of ovarian cancer cells via targeting Notch1

Neoplasma
|July 30, 2016
PubMed

Insights

MicroRNA-433 (miR-433) inhibits ovarian cancer cell migration and invasion by targeting Notch1. Down-regulation of miR-433 and up-regulation of Notch1 are linked to ovarian cancer development, suggesting Notch1 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Ovarian cancer is a leading cause of cancer-related death in women.
  • Understanding the molecular mechanisms driving ovarian cancer progression is crucial for developing effective therapies.
  • MicroRNAs (miRNAs) play significant roles in tumorigenesis, including ovarian cancer.

Purpose of the Study:

  • To investigate the role of miR-433 in ovarian cancer cell behaviors.
  • To elucidate the underlying molecular mechanisms involving Notch1.
  • To assess the therapeutic potential of targeting the miR-433/Notch1 pathway.

Main Methods:

  • Real-time PCR to quantify miR-433 and Notch1 expression in ovarian cancer tissues and cell lines.
  • Transfection of ovarian cancer cells with miR-433 mimics and Notch1 siRNA.
  • Western blot to assess Notch1 protein levels.
  • In vitro assays (CCK-8, wound healing, Transwell) to evaluate cell proliferation, migration, and invasion.
  • Bioinformatics and luciferase reporter assays to confirm the direct targeting of Notch1 by miR-433.

Main Results:

  • miR-433 was significantly down-regulated, while Notch1 was significantly up-regulated in ovarian cancer tissues.
  • Overexpression of miR-433 suppressed ovarian cancer cell migration and invasion but did not affect proliferation.
  • Notch1 was confirmed as a direct target of miR-433.
  • Down-regulation of Notch1 inhibited ovarian cancer cell invasion.

Conclusions:

  • miR-433 inhibits ovarian cancer cell migration and invasion by directly targeting and down-regulating Notch1.
  • The miR-433/Notch1 axis represents a critical pathway in ovarian cancer development.
  • Notch1 inhibition holds promise as a potential therapeutic strategy for ovarian 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...
4.2K
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...
24.5K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.4K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.8K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K
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...
8.2K