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Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer
Yingyan Han1, Zeyu Zhang1, Zhi Wang1
1Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
DNA double-strand break (DSB) repaired by homologous recombination (HR) is an essential process for breast cancer cells to survive. DNA2 nuclease acts parallel to homologous recombination (HR). Here, we investigated the detailed clinical attribute of DNA2 in breast cancer and the role of DNA2 in breast cancer cells' growth. We found that elevated expression of DNA2 was obviously linked to poor prognosis in breast cancer. Further, DNA2 expression was increased in the ER-negative group, PR-negative group, HER2-positive group, and high-grade group via analyzing 2,509 breast cancers in "cBioportal" and 3,063 breast cancer data in "bc-GenExMiner." Besides, the immunohistochemical staining in 26 breast cancer tissues also showed that elevated expression of DNA2 was correlated with ER-/PR-/HER+. To further detect the role of DNA2 in breast cancer cells, we took GESA, GO, and KEGG analyses and found that DNA2 was enriched in cell cycle and DNA replication pathways. Furthermore, silencing of DNA2 inhibited cell growth in T47D and MD-MB-231 breast cancer cells and suppressed tumor growth in vivo, indicating DNA2 functioned importantly in breast cancer progression and maybe a potential prognostic marker in breast cancer. Our research reveals that DNA2 is a biomarker for diagnosis and prognosis in breast cancer from multiple perspectives and gives a new clue for further preclinical and clinical investigation.
Insights
Elevated DNA2 nuclease expression correlates with poor breast cancer prognosis and promotes tumor growth. Silencing DNA2 inhibits cancer cell proliferation, identifying DNA2 as a potential diagnostic and prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Homologous recombination (HR) is crucial for breast cancer cell survival.
- DNA2 nuclease functions in parallel with HR in DNA double-strand break (DSB) repair.
Purpose of the Study:
- To investigate the clinical attributes of DNA2 in breast cancer.
- To determine the role of DNA2 in breast cancer cell growth and progression.
Main Methods:
- Analysis of large breast cancer datasets (cBioportal, bc-GenExMiner).
- Immunohistochemical staining of breast cancer tissues.
- Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and KEGG pathway analyses.
- In vitro cell growth assays and in vivo tumor suppression studies.
Main Results:
- Elevated DNA2 expression is linked to poor breast cancer prognosis.
- DNA2 expression is increased in ER-negative, PR-negative, HER2-positive, and high-grade breast cancers.
- DNA2 is enriched in cell cycle and DNA replication pathways.
- Silencing DNA2 inhibits breast cancer cell growth and tumor progression.
Conclusions:
- DNA2 is a potential prognostic biomarker for breast cancer.
- DNA2 plays a significant role in breast cancer progression.
- Further preclinical and clinical investigations of DNA2 are warranted.
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