MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma

K Boll1, K Reiche, K Kasack

  • 1RNomics Group, Fraunhofer IZI, Leipzig, Germany.

Oncogene
|March 7, 2012
PubMed

Insights

Three microRNAs (miR-130a, miR-203, miR-205) act as tumor suppressors in prostate cancer (PCa). These microRNAs are downregulated in cancer tissue, jointly targeting key oncogenic pathways and potentially inhibiting cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer (PCa) causes approximately 30,000 deaths annually in the US.
  • Two major oncogenic pathways, MAPK and Androgen Receptor (AR), are critical in PCa development and progression.

Purpose of the Study:

  • To investigate the role of microRNAs miR-130a, miR-203, and miR-205 in prostate carcinoma.
  • To determine if these microRNAs target and regulate the MAPK and AR signaling pathways.

Main Methods:

  • Transcriptomic analysis to identify microRNA-repressed genes.
  • Argonaute 2 (AGO2) co-immunoprecipitation and reporter assays to confirm microRNA targets.
  • Western blot analysis to assess signaling pathway activity.
  • Reconstitution of microRNAs in LNCaP PCa cells to observe effects on cell growth and apoptosis.

Main Results:

  • miR-130a, miR-203, and miR-205 were found to be downregulated in prostate cancer tissue.
  • These microRNAs directly target and repress components of the MAPK and AR signaling pathways, including AR coregulators and HRAS.
  • Reintroducing these microRNAs into PCa cells induced morphological changes, impaired cell growth, and promoted apoptosis and cell cycle arrest.

Conclusions:

  • The microRNAs miR-130a, miR-203, and miR-205 function as tumor suppressors in prostate carcinoma.
  • These microRNAs may play a crucial role in preventing the progression of prostate cancer to castration-resistant disease.

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...
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...
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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.