Related Experiment Video

Updated: May 16, 2026

A Proximal Culture Method to Study Paracrine Signaling Between Cells
08:17

A Proximal Culture Method to Study Paracrine Signaling Between Cells

Published on: August 28, 2018

MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer

Anirban K Mitra1, Marion Zillhardt, Youjia Hua

  • 1Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, IL 60611, USA.

Cancer Discovery
|November 23, 2012
PubMed
Abstract

Insights

Ovarian cancer cells reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) using microRNAs (miRNAs). Specific miRNA changes in fibroblasts drive CAF function, offering potential therapeutic targets within the tumor microenvironment.

Area of Science:

  • Oncology
  • Molecular Biology
  • MicroRNA Research

Background:

  • Cancer-associated fibroblasts (CAFs) are key components of the tumor stroma, but the mechanism of fibroblast transformation by cancer cells remains unclear.
  • MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression, and their deregulation is common in cancer.
  • The impact of cancer cell interaction on miRNA expression within resident fibroblasts is not well understood.

Purpose of the Study:

  • To investigate whether cancer cells alter miRNA expression in fibroblasts.
  • To determine if altered miRNA expression can induce fibroblast reprogramming into CAFs.
  • To identify specific miRNAs involved in the conversion of fibroblasts to CAFs in ovarian cancer.

Main Methods:

  • Comparative analysis of miRNA expression in ovarian CAFs versus normal fibroblasts.
  • Experimental manipulation of miRNA levels in fibroblasts using miRNA mimics and inhibitors.
  • Assessment of functional changes in fibroblasts following miRNA modulation.
  • Identification of target genes, including chemokines, regulated by the identified miRNAs.

Main Results:

  • Ovarian CAFs showed distinct miRNA profiles: downregulation of miR-31 and miR-214, and upregulation of miR-155 compared to normal fibroblasts.
  • Mimicking these miRNA changes converted normal fibroblasts into CAFs, while reversing the changes reverted CAFs.
  • Reprogrammed fibroblasts and patient-derived CAFs exhibited shared upregulated genes, particularly chemokines crucial for CAF function.
  • CCL5 (C-C motif ligand 5) was identified as a direct target of miR-214 and was highly upregulated.

Conclusions:

  • Ovarian cancer cells utilize miRNAs to reprogram fibroblasts into CAFs.
  • A specific set of three miRNAs can induce this fibroblast reprogramming.
  • These miRNAs represent potential therapeutic targets for modulating the tumor microenvironment.

More Related Videos

Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression12:42

Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression

Published on: August 28, 2012

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...
Abnormal Proliferation02:23

Abnormal Proliferation

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 daughter...
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...