The polo-like kinase (PLK) family of serine/threonine kinases contains five members (PLK1–5). Most PLKs are involved in cell cycle regulation and DNA damage response. However, PLK5 is different as it lacks a functional kinase domain and is not involved in cell cycle control. PLK5 remains the least-studied family member, and its role in oncogenesis remains enigmatic. Here, we identified tissues with high PLK5 expression by leveraging the Protein Atlas and GTEx databases with relevant literature and selected ovarian, lung, testis, endometrium, cervix, and fallopian tube tissues as candidates for further investigation. Subsequently, we performed immunohistochemical staining for PLK5 on multiple tissue microarrays followed by Vectra scanning and quantitative inForm analysis. This revealed consistently downregulated PLK5 expression in these cancers compared to normal tissues. To validate and extend our findings, we performed pan-cancer analysis ofPLK5expression using public RNAseq databases (TCGA and GTEx). We foundPLK5is downregulated in 18 cancer types, including our selected candidates. Interestingly, we also observed PLK5 expression remains consistently low in later stages of cancer, suggesting PLK5 may have a greater role in tumor initiation than cancer progression. Overall, our study demonstrates PLK5 downregulation in multiple cancers, highlighting its role as a tumor suppressor.
丝氨酸/苏氨酸激酶家族中的Polo样激酶(PLK)包含五个成员(PLK1–5)。大多数PLK参与细胞周期调控和DNA损伤应答,但PLK5因其缺乏功能性激酶结构域且不参与细胞周期调控而显得独特。目前PLK5仍是该家族中被研究最少的成员,其在肿瘤发生中的作用尚不明确。本研究通过整合蛋白质图谱数据库、GTEx数据库及相关文献,筛选出PLK5高表达的组织,并选定卵巢、肺、睾丸、子宫内膜、宫颈及输卵管组织作为后续研究对象。随后,我们对多组织芯片进行PLK5免疫组化染色,结合Vectra扫描与定量inForm分析,发现相较于正常组织,这些癌组织中PLK5表达均呈下调趋势。为验证并拓展这一发现,我们利用公共RNAseq数据库(TCGA和GTEx)对PLK5进行泛癌分析,结果显示包括选定组织在内的18种癌症类型中PLK5均存在下调现象。值得注意的是,我们还观察到PLK5在癌症晚期阶段持续保持低表达水平,提示PLK5可能在肿瘤起始阶段比进展阶段发挥更重要的作用。综上所述,本研究证实PLK5在多种癌症中表达下调,凸显其作为肿瘤抑制因子的潜在功能。
Potential Tumor Suppressor Role of Polo-like Kinase 5 in Cancer