CDCA2 Inhibits Apoptosis and Promotes Cell Proliferation in Prostate Cancer and Is Directly Regulated by HIF-1α Pathway
CDCA2 Inhibits Apoptosis and Promotes Cell Proliferation in Prostate Cancer and Is Directly Regulated by HIF-1α Pathway
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CDCA2 抑制前列腺癌细胞凋亡并促进细胞增殖，并受 HIF-1α 通路直接调节
DOI：
10.3389/fonc.2020.00725
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发表时间：
2020-05-19
影响因子：
4.7
通讯作者：
Ying, Ying
中科院分区：
文献类型：
--
作者：
Zhang, Yixiang;Cheng, Yingduan;Ying, Ying
前列腺癌（PCa）是一种严重的恶性肿瘤，常见于老年男性。鉴定前列腺癌中新的癌症相关基因对于了解其肿瘤发生机制和开发针对前列腺癌的新疗法具有重要意义。在这里，我们使用 RNA 测序来鉴定在 PCa 细胞系和组织中上调的特定基因。细胞分裂周期相关蛋白 (CDCA) 家族在细胞分裂和增殖中发挥着关键作用，在我们的 RNA 测序数据的 PCa 细胞系中表达上调。此外，我们发现CDCA2过表达，其蛋白水平与其组织学分级、临床分期和格里森评分呈正相关。在癌症基因组图谱 (TCGA) 数据集中，进一步发现 CDCA2 上调，并与多种癌症类型的不良预后和患者生存相关。功能研究表明，抑制CDCA2将导致体外细胞凋亡和增殖降低。 CDCA2 的沉默也抑制了体内肿瘤的生长。 CDCA2 的缺失会影响多种致癌途径，包括 MAPK 信号传导。此外，我们进一步证明CDCA2在缺氧条件下被诱导并受到HIF-1α/Smad3复合物的直接调节。因此，我们的数据表明CDCA2可以作为癌基因并受到缺氧和HIF-1α通路的调节。 CDCA2 可能是 PCa 的有用预后生物标志物和潜在治疗靶点。
Prostate cancer (PCa) is a major serious malignant tumor and is commonly diagnosed in older men. Identification of novel cancer-related genes in PCa is important for understanding its tumorigenesis mechanism and developing new therapies against PCa. Here, we used RNA sequencing to identify the specific genes, which are upregulated in PCa cell lines and tissues. The cell division cycle associated protein (CDCA) family, which plays a critical role in cell division and proliferation, is upregulated in the PCa cell lines of our RNA-Sequencing data. Moreover, we found that CDCA2 is overexpressed, and its protein level positively correlates with its histological grade, clinical stage, and Gleason Score. CDCA2 was further found to be upregulated and correlated with poor prognosis and patient survival in multiple cancer types in The Cancer Genome Atlas (TCGA) dataset. The functional study suggests that inhibition of CDCA2 will lead to apoptosis and lower proliferation in vitro. Silencing of CDCA2 also repressed tumor growth in vivo. Loss of CDCA2 affects several oncogenic pathways, including MAPK signaling. In addition, we further demonstrated that CDCA2 was induced in hypoxia and directly regulated by the HIF-1α/Smad3 complex. Thus, our data indicate that CDCA2 could act as an oncogene and is regulated by hypoxia and the HIF-1αpathway. CDCA2 may be a useful prognostic biomarker and potential therapeutic target for PCa.