Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Dis Markers. 2021 Jan 26;2021:8860728. doi: 10.1155/2021/8860728. eCollection 2021.
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 , 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.
DNA 双链断裂(DSB)通过同源重组(HR)修复是乳腺癌细胞存活的必要过程。DNA2 核酸酶与同源重组(HR)平行作用。在这里,我们研究了 DNA2 在乳腺癌中的详细临床特征以及其在乳腺癌细胞生长中的作用。我们发现 DNA2 的高表达与乳腺癌的不良预后明显相关。进一步通过分析“cBioportal”中的 2509 例乳腺癌和“bc-GenExMiner”中的 3063 例乳腺癌数据,我们发现 DNA2 的表达在 ER-阴性组、PR-阴性组、HER2-阳性组和高级组中增加。此外,26 例乳腺癌组织的免疫组织化学染色也表明 DNA2 的高表达与 ER-/PR-/HER+相关。为了进一步检测 DNA2 在乳腺癌细胞中的作用,我们进行了 GESA、GO 和 KEGG 分析,发现 DNA2 富集在细胞周期和 DNA 复制途径中。此外,沉默 DNA2 抑制了 T47D 和 MD-MB-231 乳腺癌细胞的生长,并抑制了肿瘤的生长,表明 DNA2 在乳腺癌的进展中起着重要作用,可能是乳腺癌的一个潜在预后标志物。我们的研究从多个角度揭示了 DNA2 是乳腺癌诊断和预后的生物标志物,并为进一步的临床前和临床研究提供了新的线索。