CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis

Xiyu Dai1,2, Xinan Chen1,2, Wensun Chen1,2

  • 1Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Epigenetics
|February 25, 2023
PubMed

Insights

Circular RNA DHRS3 (circDHRS3) is underexpressed in prostate cancer. Overexpressing circDHRS3 inhibits cancer growth and metastasis by targeting miR-421 and MEIS2, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer is a leading global cancer in men.
  • Circular RNAs (circRNAs) are increasingly recognized for their role in cancer malignancy.
  • Understanding circRNA function is crucial for developing new prostate cancer therapies.

Purpose of the Study:

  • To investigate the role and mechanism of circDHRS3 in prostate cancer.
  • To explore circDHRS3 as a potential biomarker and therapeutic target.

Main Methods:

  • circRNA sequencing and quantitative real-time PCR (qRT-PCR) for expression analysis.
  • In vitro assays (CCK-8, colony formation, wound-healing) and in vivo xenograft models in BALB/c Nude mice.
  • Molecular mechanism studies including RIP assay, FISH, RNA pulldown, dual-luciferase, and rescue assays.

Main Results:

  • circDHRS3 expression was found to be low in prostate cancer tissues.
  • Overexpression of circDHRS3 suppressed prostate cancer cell proliferation and migration in vitro.
  • circDHRS3 targets miR-421, and the circDHRS3/miR-421/MEIS2 axis regulates cancer cell proliferation and metastasis.
  • In vivo studies confirmed circDHRS3 inhibits lung and bone metastasis of prostate cancer cells.

Conclusions:

  • circDHRS3 acts as a tumor suppressor in prostate cancer.
  • The circDHRS3/miR-421/MEIS2 pathway is a key mechanism driving prostate cancer progression.
  • circDHRS3 holds promise as a diagnostic biomarker and therapeutic target for advanced 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...
4.8K
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...
4.6K
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...
21.5K
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...
3.8K
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...
6.6K
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.
35.5K