miR-154 inhibits prostate cancer cell proliferation by targeting CCND2

Chen Zhu1, Pengfei Shao1, Meiling Bao1

  • 1State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Urologic Oncology
|February 23, 2013
PubMed
Abstract

Insights

MicroRNA-154 (miR-154) suppresses prostate cancer (CaP) cell growth and proliferation by targeting CCND2. This finding suggests miR-154 as a potential therapeutic target for prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer (CaP) exhibits reduced levels of miR-154.
  • The specific role and mechanisms of miR-154 in CaP remain unclear.

Purpose of the Study:

  • Investigate the functional role of miR-154 in CaP cells.
  • Identify molecular targets regulated by miR-154.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure miR-154 expression.
  • In vitro assays (CCK-8, colony formation, flow cytometry) to assess CaP cell growth and proliferation upon miR-154 restoration.
  • Luciferase reporter assay to confirm direct binding of miR-154 to the 3'-untranslated region of CCND2.

Main Results:

  • miR-154 expression was significantly lower in primary CaP samples than in nonmalignant samples.
  • Restoring miR-154 levels inhibited CaP cell growth and proliferation in vitro.
  • miR-154 was found to directly down-regulate CCND2 expression by binding to its 3'-untranslated region.

Conclusions:

  • miR-154 suppresses prostate cancer proliferation by inhibiting CCND2.
  • miR-154 represents a potential novel therapeutic strategy for prostate cancer.

Related Concept Videos

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...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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.