Related Experiment Video

Updated: May 25, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

7.5K

MicroRNA profiling identifies VHL/HIF-2α dependent miR-2355-5p as a key modulator of clear cell Renal cell carcinoma

Patric M Page1,2, Sonia A Dastous1,2, Patrick O Richard3,4

  • 1Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet, Moncton, NB, E1A 3E9, Canada.

Cancer Cell International
|February 27, 2025
PubMed

Insights

In clear cell renal cell carcinoma (ccRCC), the VHL gene inactivation leads to miR-2355-5p overexpression, promoting tumor growth and angiogenesis. Targeting this microRNA (miRNA) inhibited ccRCC progression in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is a key event in clear cell renal cell carcinoma (ccRCC) development.
  • VHL loss leads to Hypoxia-Induced Factor (HIFα) accumulation, which influences microRNA (miRNA) expression and promotes ccRCC tumorigenesis.

Purpose of the Study:

  • To identify VHL-dependent miRNAs in ccRCC.
  • To investigate the role of miR-2355-5p in ccRCC tumorigenesis, angiogenesis, and its potential as a therapeutic target.

Main Methods:

  • miRNA profiling and high-throughput analysis to identify VHL-dependent miRNAs.
  • Validation in ccRCC cell models, primary tumors, and patient plasma.
  • CRISPR/Cas9 targeting of miR-2355-5p in vitro and in vivo (mouse xenograft models).
  • miRNA pulldown assay to identify target genes.

Main Results:

  • miR-2355-5p was significantly overexpressed in ccRCC cell models, primary tumors, and patient plasma.
  • miR-2355-5p overexpression is dependent on HIF-2α.
  • Targeting miR-2355-5p with CRISPR/Cas9 inhibited angiogenesis, reduced cell proliferation, and decreased tumor growth in vivo.
  • Five tumor suppressor genes (ACO1, BTG2, CMTM4, SLIT2, WDFY2) were identified as direct targets of miR-2355-5p and were downregulated in ccRCC.

Conclusions:

  • miR-2355-5p acts as an oncogenic miRNA in VHL-deficient ccRCC.
  • miR-2355-5p plays a critical role in regulating angiogenesis and tumor growth.
  • miR-2355-5p is a potential diagnostic biomarker and therapeutic target for ccRCC.
Keywords:
AngiogenesisHIFTumor growthVHLccRCCmiR-2355-5pmiRNAs

More Related Videos

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells06:48

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells

Published on: June 16, 2022

1.9K
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

17.5K

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...
3.0K
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...
4.4K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.5K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.8K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K