MicroRNA-135a-3p is downregulated and serves as a tumour suppressor in ovarian cancer by targeting CCR2

Shufeng Duan1, Xuecai Dong1, Jing Hai1

  • 1Department of Gynecology and Oncology, Xinxiang Central Hospital, Xinxiang, Henan, 453000, China.

Insights

MicroRNA-135a-3p acts as a tumor suppressor in ovarian cancer. Its downregulation promotes cancer cell growth and metastasis by targeting C-C chemokine receptor type 2 (CCR2).

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators in cancer development.
  • miR-135a family members, including miR-135a-5p and miR-135a-3p, show tumor-suppressive roles in various cancers.
  • The specific function and molecular mechanisms of miR-135a-3p in ovarian cancer remain unclear.

Purpose of the Study:

  • To investigate the role of miR-135a-3p in ovarian carcinoma.
  • To elucidate the molecular mechanisms by which miR-135a-3p affects ovarian cancer cell growth and metastasis.

Main Methods:

  • Quantitative analysis of miR-135a-3p expression in ovarian cancer tissues.
  • In vitro assays assessing the effects of miR-135a-3p overexpression on cell proliferation, migration, and invasion.
  • Luciferase reporter assays to identify miR-135a-3p targets.
  • In vivo studies using xenograft models.

Main Results:

  • miR-135a-3p expression is significantly downregulated in ovarian carcinoma tissues.
  • Overexpression of miR-135a-3p inhibits ovarian cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
  • C-C chemokine receptor type 2 (CCR2) is identified as a direct target of miR-135a-3p.
  • CCR2 depletion mimics miR-135a-3p's inhibitory effects, and CCR2 overexpression rescues these effects.
  • miR-135a-3p suppresses tumor growth in vivo by targeting CCR2.

Conclusions:

  • miR-135a-3p functions as a tumor suppressor gene in ovarian cancer.
  • The tumor-suppressive role of miR-135a-3p is mediated through the regulation of CCR2.
  • miR-135a-3p represents a potential therapeutic target for ovarian cancer treatment.

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...
24.2K
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 the pre-miRNA...
4.0K
Self-Serving Bias01:29

Self-Serving Bias

Self-serving bias is a cognitive phenomenon in which individuals attribute positive outcomes to internal factors such as their abilities, intelligence, or effort while attributing negative outcomes to external circumstances. This cognitive distortion helps maintain self-esteem but can also impede objective self-assessment.Theoretical Explanations of Self-Serving BiasTwo primary theories explain the self-serving bias: the cognitive explanation and the motivational explanation.The cognitive...
240
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.8K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.9K