The Affiliated Stomatological Hospital of Nanchang University, The Key Laboratory of Oral Biomedicine, Jiangxi Province, Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, 330006, Jiangxi Province, China.
The First Affiliated Hospital of Nanchang University, Nanchang City, 330006, Jiangxi Province, China.
Dis Markers. 2022 Apr 22;2022:3398492. doi: 10.1155/2022/3398492. eCollection 2022.
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of head and neck squamous cell carcinoma (HNSCC), but the causes and molecular mechanisms remain unclear. The wingless-integrated/-catenin (WNT/-catenin) signaling pathway plays a vital role in cancer cell proliferation, differentiation, and metastasis, including OSCC. To screen potential -catenin-associated genes involved in OSCC, the intersection of these genes in the STRING and IMEx databases was assessed using differential expression genes (DEG) from public microarrays, and 22 were further selected to construct a -catenin-protein interaction network. The top 14 hub genes (node degree > 10) within the network were selected. Pearson's correlation analysis showed that -catenin expression correlated positively with the expression of 11 genes, including , , , , , , , , , , and . A heat map of overall hub gene survival was created, and elevated expression of DKK1 and RUVBL1 was associated with poor survival using the Mantel-Cox test. To identify the function of RUVBL1, colony formation assay, transwell assay, and western blotting revealed that knock-down of RUVBL1 by siRNA decreased H157 and Cal-27 cell proliferation and metastasis by inhibiting -catenin signaling. These findings suggest that RUVBL1 may serve as a diagnostic and prognostic biomarker for OSCC, as well as a therapeutic target, and may help to uncover additional molecular mechanisms of -catenin-driven OSCC tumorigenesis.
口腔鳞状细胞癌（OSCC）是头颈部鳞状细胞癌（HNSCC）中最常见的恶性肿瘤，但病因和分子机制尚不清楚。Wnt/-连环蛋白（WNT/-catenin）信号通路在包括 OSCC 在内的癌细胞增殖、分化和转移中起着至关重要的作用。为了筛选潜在的与 OSCC 相关的 -连环蛋白相关基因，使用来自公共微阵列的差异表达基因（DEG）评估了 STRING 和 IMEx 数据库中的这些基因的交集，并进一步选择了 22 个基因来构建 -连环蛋白蛋白相互作用网络。选择网络中前 14 个高节点度（节点度>10）的基因。Pearson 相关性分析显示，-连环蛋白表达与 11 个基因的表达呈正相关，包括、、、、、、、、、和。创建了总体枢纽基因生存的热图，Mantel-Cox 检验显示 DKK1 和 RUVBL1 的高表达与生存不良相关。为了鉴定 RUVBL1 的功能，通过集落形成试验、Transwell 试验和 Western blot 发现，通过 siRNA 敲低 RUVBL1 可通过抑制 -连环蛋白信号抑制 H157 和 Cal-27 细胞的增殖和转移。这些发现表明 RUVBL1 可能作为 OSCC 的诊断和预后生物标志物，以及治疗靶点，并可能有助于揭示 -连环蛋白驱动的 OSCC 肿瘤发生的其他分子机制。
