BRD7-Mediated miR-3148 Inhibits Progression of Cervical Cancer by Targeting Wnt3a/β-Catenin Pathway

Haiyan Wang1, Yun Xie2

  • 1Department of Gynaecology, Qinghai University Affiliated Hospital, Xining, 810001, Qinghai, China.

Insights

MicroRNA-3148 (miR-3148) acts as a tumor suppressor in cervical cancer by inhibiting cell proliferation and promoting apoptosis. Its expression is regulated by bromodomain containing 7 (BRD7) and it targets Wnt3a, impacting the Wnt3a/β-catenin pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) play crucial roles in tumor development, but their specific functions and mechanisms in many cancers, including cervical cancer, remain incompletely understood.
  • Identifying novel miRNAs and elucidating their regulatory pathways are essential for advancing cancer diagnostics and therapeutics.

Purpose of the Study:

  • To investigate the role and mechanism of miR-3148 in cervical cancer.
  • To identify upstream regulators and downstream targets of miR-3148 in cervical cancer cells.

Main Methods:

  • Quantitative real-time PCR to assess miR-3148 expression.
  • Cell proliferation assays and apoptosis assays to evaluate the functional role of miR-3148.
  • Western blotting and luciferase reporter assays to explore the regulatory mechanism at transcriptional and post-transcriptional levels.

Main Results:

  • miR-3148 was found to be downregulated in cervical cancer.
  • Upregulation of miR-3148 inhibited cervical cancer cell proliferation and induced apoptosis, confirming its tumor suppressor function.
  • Bromodomain containing 7 (BRD7) was identified as a transcriptional activator of miR-3148.
  • miR-3148 directly targets Wnt3a mRNA, inhibiting Wnt3a expression and subsequently suppressing the Wnt3a/β-catenin signaling pathway.

Conclusions:

  • miR-3148 functions as a tumor suppressor in cervical cancer.
  • The BRD7/miR-3148/Wnt3a/β-catenin axis represents a critical regulatory pathway in cervical cancer progression.
  • This pathway offers a potential target for novel therapeutic strategies in cervical cancer treatment.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.2K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
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...
5.5K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.9K
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...
23.8K
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...
3.6K