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Target: PRIM2


Research on PRIM2

1. Target Summary:

PRIM2 (DNA primase subunit 2) is a crucial enzyme involved in DNA replication and repair processes. It is part of the DNA polymerase alpha-primase complex, which synthesizes RNA primers necessary for DNA polymerases to initiate DNA synthesis. PRIM2 has been implicated in various cancers, including lung cancer, pancreatic ductal adenocarcinoma, and gliomas, where its overexpression is associated with poor prognosis and aggressive disease progression.

2. Mechanism:

PRIM2 functions as a primase, synthesizing short RNA primers that are essential for DNA replication. It operates within a heterotetrameric complex with DNA polymerase alpha, facilitating the transition from primer synthesis to DNA elongation. The C-terminal domain of PRIM2 is critical for its interaction with DNA and the regulation of primer length.
In cancer, PRIM2 is often overexpressed, which can lead to increased cell proliferation and tumor growth. For instance, in lung cancer, PRIM2 expression is regulated by the p53/RB pathway, where mutations in p53 lead to elevated PRIM2 levels, promoting cell cycle progression and DNA replication (Wang et al., 2022, PMID: 35884433). Additionally, PRIM2 has been shown to interact with other proteins, such as FAM111B, to enhance cancer cell proliferation and metastasis (Yin et al., 2024, PMID: 39556158).

3. Approved Drugs:

Currently, there are no specific drugs approved that directly target PRIM2. However, compounds like Dihydroartemisinin (DHA) have been shown to inhibit PRIM2 expression and induce ferroptosis in lung cancer cells, suggesting a potential therapeutic avenue (Yuan et al., 2020, PMID: 33149601).

4. Hypotheses:

  1. PRIM2 as a Therapeutic Target: Targeting PRIM2 could reduce tumor growth and improve patient outcomes in cancers characterized by its overexpression.
  2. Biomarker for Aggressiveness: PRIM2 expression levels may serve as a biomarker for predicting cancer aggressiveness and treatment response.
  3. Role in Resistance: Variations in PRIM2 expression may contribute to resistance against certain cancer therapies, such as cetuximab in colorectal cancer (Kim et al., 2021, PMID: 34315006).

5. Validation:

The role of PRIM2 in cancer has been validated through various studies demonstrating its overexpression in multiple cancer types and its association with poor prognosis. For example, in gliomas, PRIM2 has been identified as a marker of MYC-driven hyper-proliferation and is linked to aggressive disease states (Sun et al., 2024, PMID: 38423596). Additionally, the inhibition of PRIM2 has been shown to induce cell cycle arrest and apoptosis in cancer cell lines (Wang et al., 2022, PMID: 35884433).

6. Clinical Trials:

While specific clinical trials targeting PRIM2 are not yet available, ongoing research is exploring the therapeutic implications of inhibiting PRIM2 in various cancers. Future studies may focus on the efficacy of drugs like DHA in clinical settings.

7. Involved Pathways:

PRIM2 is primarily involved in the following pathways:
  • DNA Replication Pathway: Facilitates the synthesis of RNA primers necessary for DNA polymerases.
  • Cell Cycle Regulation: Its expression is regulated by the p53/RB pathway, influencing cell cycle progression.
  • Ferroptosis Pathway: Inhibition of PRIM2 has been linked to the induction of ferroptosis in cancer cells (Yuan et al., 2020, PMID: 33149601).

8. Associated Genes:

  • FAM111B: Interacts with PRIM2 to promote cancer cell proliferation (Yin et al., 2024, PMID: 39556158).
  • MYC: Regulates PRIM2 expression in gliomas, linking it to aggressive tumor behavior (Sun et al., 2024, PMID: 38423596).
  • p53: Mutations in p53 lead to increased PRIM2 expression, promoting tumor progression (Wang et al., 2022, PMID: 35884433).

9. Target Expression:

PRIM2 is often overexpressed in various cancers, including lung cancer, pancreatic cancer, and gliomas. Its expression levels correlate with tumor aggressiveness and poor patient outcomes (Wang et al., 2022, PMID: 35884433; Sun et al., 2024, PMID: 38423596).

10. Additional Context:

PRIM2's role in cancer biology highlights its potential as a therapeutic target and biomarker. Understanding its mechanisms and interactions within cancer pathways can lead to novel treatment strategies and improved patient management.

11. References:

  • Wang, T., Tang, T., & Jiang, Y. (2022). PRIM2 Promotes Cell Cycle and Tumor Progression in p53-Mutant Lung Cancer. Cancers. PMID: 35884433.
  • Yin, J., Qin, F., & Chen, H. (2024). PRIM2 promotes proliferation and metastasis of pancreatic ductal adenocarcinoma through interactions with FAM111B. Medical Oncology. PMID: 39556158.
  • Yuan, B., Liao, F., & Shi, Z.Z. (2020). Dihydroartemisinin Inhibits the Proliferation, Colony Formation and Induces Ferroptosis of Lung Cancer Cells by Inhibiting PRIM2/SLC7A11 Axis. OncoTargets and Therapy. PMID: 33149601.
  • Sun, R., Shao, X., & Akter, F. (2024). PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients. Cancer Genomics & Proteomics. PMID: 38423596.
  • Kim, S.Y., Kim, K., & Cho, S.H. (2021). Longitudinal change of genetic variations in cetuximab-treated metastatic colorectal cancer. Cancer Genetics. PMID: 34315006.