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Target: POLA2


Research on the Target POLA2

1. Target Summary:

POLA2 (DNA polymerase alpha-primase complex subunit 2) is a crucial component of the DNA polymerase alpha-primase complex, which is essential for DNA replication and repair. It plays a significant role in various cancers, including hepatocellular carcinoma (HCC), colon cancer, and lung cancer. POLA2 is implicated in cell proliferation, migration, and apoptosis, making it a potential target for therapeutic intervention.

2. Mechanism:

POLA2 functions as an accessory subunit of the DNA polymerase alpha-primase complex, which is responsible for synthesizing RNA primers and initiating DNA replication. The interaction between POLA2 and other components of the complex is vital for the proper functioning of DNA replication.
  • Circ-POLA2: A circular RNA derived from POLA2 has been shown to regulate cancer cell activities through various pathways, including the miR-138-5p/SEMA4C axis in colon cancer, promoting cell proliferation and migration (Huang et al., 2023, PMID: 37595073).
  • Cell Cycle Regulation: POLA2 is involved in regulating the cell cycle, particularly in hepatocellular carcinoma, where its expression correlates with cell proliferation and tumor progression (Yang et al., 2024, PMID: 37861044).
  • Immune Infiltration: POLA2 expression is associated with immune cell infiltration in tumors, suggesting a role in the tumor microenvironment and potential implications for immunotherapy (Liu et al., 2023, PMID: 37452331).

3. Approved Drugs:

Currently, there are no specific drugs approved that directly target POLA2. However, understanding its role in DNA replication and repair may lead to the development of targeted therapies in the future.

4. Hypotheses:

  • Role in Cancer Progression: POLA2 may serve as a key factor in the progression of various cancers, including HCC, by regulating cell proliferation and the cell cycle (Yang et al., 2024, PMID: 37861044).
  • Therapeutic Target: Targeting POLA2 could enhance the efficacy of existing cancer treatments, particularly in overcoming drug resistance mechanisms (Koh et al., 2016, PMID: 28155658).
  • Biomarker Potential: POLA2 may act as a prognostic biomarker for cancer progression and treatment response, particularly in HCC (Liu et al., 2023, PMID: 37452331).

5. Validation:

  • Expression Studies: Studies have shown that POLA2 is overexpressed in various cancers, including HCC, and its knockdown leads to reduced cell proliferation and increased apoptosis (Yang et al., 2024, PMID: 37861044).
  • Functional Assays: Functional assays, such as CCK-8 and colony formation assays, have demonstrated that POLA2 knockdown inhibits cancer cell growth (Yang et al., 2024, PMID: 37861044).
  • Correlation with Immune Markers: POLA2 expression has been correlated with immune cell markers, indicating its potential role in the tumor microenvironment (Liu et al., 2023, PMID: 37452331).

6. Clinical Trials:

As of now, there are no specific clinical trials targeting POLA2 directly. However, ongoing research is exploring its role in cancer biology and potential therapeutic implications.

7. Involved Pathways:

  • PI3K/AKT/mTOR Pathway: POLA2 has been implicated in the regulation of the PI3K/AKT/mTOR signaling pathway, which is crucial for cell growth and survival (Yang et al., 2024, PMID: 37861044).
  • DNA Repair Pathways: POLA2 is involved in DNA replication and repair mechanisms, which are critical for maintaining genomic stability in cancer cells.

8. Associated Genes:

  • CircRNAs: Circ-POLA2 has been identified as a significant regulator in cancer, influencing various signaling pathways (Huang et al., 2023, PMID: 37595073).
  • Other Polymerases: POLA2 interacts with other DNA polymerases and repair proteins, contributing to the overall DNA replication process.

9. Target Expression:

POLA2 is highly expressed in various cancers, including HCC, colon cancer, and lung cancer. Its expression levels correlate with tumor progression and patient prognosis (Liu et al., 2023, PMID: 37452331; Yang et al., 2024, PMID: 37861044).

10. Additional Context:

Understanding POLA2's role in cancer biology is crucial for developing targeted therapies. Its involvement in DNA replication and repair, along with its association with immune infiltration, positions it as a potential target for future cancer treatments.

11. References:

  1. Huang, Y., Bai, Q., & Yu, H. (2023). Circ-POLA2-mediated miR-138-5p/SEMA4C axis affects colon cancer cell activities. Acta biochimica Polonica, PMID: 37595073.
  2. Yang, Z., Shen, X., & Wang, Z. (2024). The Biological Function of POLA2 in Hepatocellular Carcinoma. Combinatorial chemistry & high throughput screening, PMID: 37861044.
  3. Liu, L., Wang, Q., & Wu, L. (2023). Overexpression of POLA2 in hepatocellular carcinoma is involved in immune infiltration and predicts a poor prognosis. Cancer cell international, PMID: 37452331.
  4. Koh, V., Kwan, H.Y., & Tan, W.L. (2016). Knockdown of POLA2 increases gemcitabine resistance in lung cancer cells. BMC genomics, PMID: 28155658.
  5. Kvarnung, M., Pettersson, M., & Chun-On, P. (2024). Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder. European journal of human genetics, PMID: 39616267.
This comprehensive overview of POLA2 highlights its significance in cancer biology and potential as a therapeutic target, paving the way for future research and clinical applications.