EIF4A3-Mediated circ_0008126 Inhibits the Progression and Metastasis of Gastric Cancer by Modulating the

Zeen Wang1, Wenxing Chen1, Ziwei Wang1

  • 1Gastrointestinal Surgical Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Cancers
|January 25, 2025
PubMed
Abstract

Insights

Circular RNA circ_0008126 is downregulated in gastric cancer (GC) and inhibits tumor progression. EIF4A3-mediated circ_0008126 regulates APC expression and inactivates the beta-catenin pathway, suppressing GC development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized as key regulators in tumor progression.
  • The specific role and underlying mechanisms of circ_0008126 in gastric cancer (GC) remain largely unexplored.

Purpose of the Study:

  • To investigate the expression levels and clinical significance of circ_0008126 in GC.
  • To elucidate the biological functions and molecular mechanisms of circ_0008126 in GC progression.

Main Methods:

  • In vitro and in vivo experiments were conducted to assess GC phenotypes.
  • Mechanisms involving miR-502-5p, EIF4A3, and APC were explored using RNA pull-down, dual-luciferase reporter assays, RIP, and RNA FISH.

Main Results:

  • Circ_0008126 expression was significantly downregulated in GC tissues and cells, correlating with advanced stage and poor prognosis.
  • Circ_0008126 suppressed GC cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT).
  • EIF4A3 mediates circ_0008126 formation; circ_0008126 binds miR-502-5p to regulate APC expression and inactivate the beta-catenin pathway, enhancing APC mRNA stability.

Conclusions:

  • EIF4A3-mediated circ_0008126 inhibits gastric cancer tumorigenesis and development.
  • Circ_0008126 acts by regulating APC expression and inactivating the beta-catenin pathway via interactions with miR-502-5p and EIF4A3.

Related Concept Videos

Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
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...
3.7K
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...
4.6K
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...
6.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K