Related Experiment Video

Updated: May 24, 2026

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

Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect

Marco Gerlinger1, Claudio R Santos, Bradley Spencer-Dene

  • 1Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields, London, WC2A 3LY, UK.

The Journal of Pathology
|February 25, 2012
PubMed

Insights

Targeting monocarboxylate transporter MCT4 (SLC16A3) could be a new strategy for clear cell renal cell carcinoma (ccRCC). Silencing MCT4 in ccRCC cells impacts metabolism, survival, and disease progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype.
  • Identifying novel therapeutic targets is crucial for improving ccRCC outcomes.

Purpose of the Study:

  • To identify new therapeutic targets for ccRCC by integrating RNA interference screening with gene expression analysis.
  • To investigate the role of monocarboxylate transporter MCT4 (SLC16A3) as a potential therapeutic target in ccRCC.

Main Methods:

  • Genome-wide RNA interference screen for ccRCC survival regulators.
  • Meta-analysis of ccRCC expression datasets to identify overexpressed genes.
  • MCT4 silencing in ccRCC cell lines and analysis of metabolic and cellular effects.
  • Analysis of MCT4 protein expression in primary and metastatic ccRCC tissues.

Main Results:

  • MCT4 (SLC16A3) was identified as a potent survival regulator and is highly overexpressed in ccRCC.
  • MCT4 silencing impaired ccRCC cell viability, lactate secretion, and induced cell cycle arrest and apoptosis.
  • MCT4 silencing led to intracellular acidosis, reduced ATP production, and partial reversion of the Warburg effect.
  • Higher MCT4 expression correlated with poorer relapse-free survival and higher Fuhrman nuclear grade in ccRCC.
  • MCT4 expression was elevated in metastatic ccRCC compared to primary tumors.

Conclusions:

  • MCT4 is a significant survival regulator in ccRCC and a potential therapeutic target.
  • Targeting MCT4 may reverse the Warburg effect and limit ccRCC progression.
  • MCT4 expression levels can serve as a prognostic biomarker in ccRCC.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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...