Downregulated NOX4 underlies a novel inhibitory role of microRNA-137 in prostate cancer

Qi-Quan Wu1, Bin Zheng1, Guo-Bin Weng1

  • 1Department of Urology Surgery, Ningbo Yinzhou No. 2 Hospital, Ningbo, People's Republic of China.

Insights

MicroRNA-137 (miR-137) inhibits prostate cancer progression by downregulating NADPH oxidase 4 (NOX4), suppressing glycolysis, and promoting apoptosis. This suggests miR-137 as a potential therapeutic target for prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer is a leading cause of cancer-related deaths in males.
  • MicroRNAs (miRs) are implicated in carcinogenesis, but their specific roles in prostate cancer require further investigation.
  • NADPH oxidase 4 (NOX4) is a potential regulator in cancer pathways.

Purpose of the Study:

  • To investigate the role of miR-137 in prostate cancer.
  • To explore the regulatory relationship between miR-137 and NOX4 in prostate cancer.
  • To determine the impact of miR-137 on cancer cell metabolism, proliferation, and apoptosis.

Main Methods:

  • Microarray analysis to identify differentially expressed genes and miRs.
  • Detection of miR-137 and NOX4 expression and their target relationship.
  • Transfection of PC-3 cells with siNOX4 and miR-137 mimic.
  • Evaluation of glycolysis, cell viability, proliferation, and apoptosis markers.

Main Results:

  • miR-137 expression was downregulated, while NOX4 expression was upregulated in prostate cancer tissues.
  • NOX4 was identified as a direct target gene of miR-137.
  • Overexpression of miR-137 or silencing of NOX4 reduced NOX4 and Bcl-2 expression.
  • miR-137 overexpression and NOX4 silencing decreased glycolysis, cell proliferation, and ATP production.
  • Apoptosis markers (caspases 3, 8, 9, cytochrome c, cleaved PARP, Bax) were increased, while Bcl-2 was decreased.

Conclusions:

  • miR-137 plays a critical role in suppressing prostate cancer progression by regulating NOX4.
  • miR-137 inhibits glycolysis and promotes apoptosis in prostate cancer cells via NOX4.
  • Targeting the miR-137/NOX4 pathway offers a potential therapeutic strategy for prostate cancer treatment.

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...
24.2K
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...
4.0K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.8K
Excitatory and Inhibitory Effects of Neurotransmitters01:29

Excitatory and Inhibitory Effects of Neurotransmitters

When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
12.9K
Role of Septins01:02

Role of Septins

Septins are the recently discovered fourth major protein component of the cytoskeleton, along with microfilaments, microtubules, and intermediate filaments. These proteins can associate with other cytoskeletal filaments and carry out varied roles or can be free-floating in the cytoplasm.
Cellular Functions of Septins
Recent studies have revealed the multifaceted roles of septins in various cellular processes such as cytokinesis, ciliogenesis, and neurogenesis. Septins act as scaffolds and...
2.2K
The Role of Culture01:23

The Role of Culture

Culture plays a crucial role in shaping self-identity and influencing thought and behavior, a foundational interest within social psychology. The multicultural perspective recognizes that individuals do not exist in a vacuum; instead, their experiences, perceptions, and actions are deeply influenced by the intersecting dimensions of their cultural, ethnic, and social group affiliations.Cultural Influence on Self-Identity and Social PerceptionCultural frameworks inform how individuals define...
412