Tumor-suppressive microRNA-143/145 cluster targets hexokinase-2 in renal cell carcinoma

Related Experiment Video

Updated: May 7, 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

Hirofumi Yoshino1, Hideki Enokida, Toshihiko Itesako

  • 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Cancer Science
|September 17, 2013
PubMed

Insights

The miR-143/145 microRNA cluster acts as a tumor suppressor in kidney cancer (RCC). Its downregulation promotes cancer growth by increasing the oncogene hexokinase-2 (HK2).

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNA (miRNA) expression signatures are crucial in cancer research.
  • The miR-143/145 cluster is frequently downregulated in various cancers, suggesting a tumor-suppressive role.
  • Renal cell carcinoma (RCC) is a significant health concern with complex molecular underpinnings.

Purpose of the Study:

  • To investigate the functional role of the miR-143/145 cluster in renal cell carcinoma (RCC).
  • To identify novel molecular targets of the miR-143/145 cluster in RCC.
  • To elucidate the mechanism by which miR-143/145 influences RCC progression.

Main Methods:

  • Quantitative real-time PCR to assess miR-143 and miR-145 expression in RCC tissues and cell lines.
  • Cell proliferation and invasion assays following miRNA restoration or gene silencing.
  • Bioinformatic analysis and luciferase reporter assays to identify and validate miR-143/145 targets.
  • Western blotting to confirm protein expression levels.

Main Results:

  • miR-143 and miR-145 were significantly downregulated in RCC tissues compared to non-cancerous tissues.
  • Restoration of miR-143 or miR-145 inhibited proliferation and invasion of RCC cells, confirming their tumor-suppressive function.
  • Hexokinase-2 (HK2), a key glycolytic enzyme, was identified as a direct target of miR-143/145.
  • HK2 expression was elevated in RCC tissues and its silencing suppressed RCC cell growth and invasion.

Conclusions:

  • The miR-143/145 cluster functions as a tumor suppressor in renal cell carcinoma.
  • Loss of miR-143/145 promotes RCC progression by upregulating the oncogenic target hexokinase-2 (HK2).
  • Targeting the miR-143/145-HK2 axis presents a potential therapeutic strategy for renal cell carcinoma.

More Related Videos

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

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 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...
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...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...