Accumulating evidence shows that Parkinson’s disease is negatively associated with colon cancer risk, indicating that Parkinson’s disease family proteins may be involved in the initiation of colon cancer. Here, we aimed to identify a Parkinson’s disease-related gene involved in colon cancer, elucidate the underlying mechanisms, and test whether it can be used as a target for cancer therapy. We first screened colon cancer and normal tissues for differential expression of Parkinson’s disease-associated genes and identified ATP13A2, which encodes cation-transporting ATPase 13A2, as a putative marker for colon cancer. We next correlated ATP13A2 expression with colon cancer prognosis. We performed a series of ATP13A2 knockdown and overexpression studies in vitro to identify the contribution of ATP13A2 in the stemness and invasive capacity of colon cancer cells. Additionally, autophagy flux assay were determined to explore the mechanism of ATP13A2 induced stemness. Finally, we knocked down ATP13A2 in mice using siRNA to determine whether it can be used as target for colon cancer treatment. Colon cancer patients with high ATP13A2 expression exhibit shorter overall survival than those with low ATP13A2. Functionally, ATP13A2 acts as a novel stimulator of stem-like traits. Furthermore, knockdown of ATP13A2 in HCT116 resulted in decreased levels of cellular autophagy. Additionally, bafilomycin A1, an autophagy inhibitor, reversed the ATP13A2-induced stemness of colon cancer cells. Lastly treatment with ATP13A2 siRNA reduced the volume of colon cancer xenografts in mice. The PD-associated gene ATP13A2 is involved in colon cancer stemness through regulation of autophagy. Furthermore, ATP13A2 is a novel prognostic biomarker for colon cancer and is a potential target for colon cancer therapy.

中文翻译：

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帕金森氏病相关基因ATP13A2的敲低可通过阻断结肠癌的自噬通量来减少肿瘤发生

越来越多的证据表明帕金森氏病与结肠癌风险呈负相关，表明帕金森氏病家族蛋白可能与结肠癌的发生有关。在这里，我们旨在鉴定与结肠癌有关的帕金森氏病相关基因，阐明其潜在机制，并测试其是否可用作癌症治疗的靶标。我们首先筛查了结肠癌和正常组织中帕金森氏病相关基因的差异表达，并确定了ATP13A2（其编码阳离子转运ATPase 13A2）作为结肠癌的假定标记。接下来，我们将ATP13A2表达与结肠癌的预后相关联。我们在体外进行了一系列ATP13A2敲低和过表达研究，以确定ATP13A2对结肠癌细胞的干性和侵袭能力的贡献。此外，自噬通量测定以确定ATP13A2诱导干的机制。最后，我们使用siRNA敲除了小鼠中的ATP13A2，以确定其是否可用作结肠癌治疗的靶标。具有高ATP13A2表达的结肠癌患者的总生存期比具有低ATP13A2的结肠癌患者的生存期短。在功能上，ATP13A2充当茎干性状的新型刺激物。此外，HCT116中ATP13A2的敲低导致细胞自噬水平降低。此外，自噬抑制剂bafilomycin A1逆转了ATP13A2诱导的结肠癌细胞的干性。最后，用ATP13A2 siRNA进行处理可减少小鼠结肠癌异种移植的体积。PD相关基因ATP13A2通过自噬调节参与结肠癌的干性。此外，ATP13A2是结肠癌的一种新的预后生物标志物，并且是结肠癌治疗的潜在靶标。