Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Department of Pancreatic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Arch Biochem Biophys. 2022 Sep 30;727:109323. doi: 10.1016/j.abb.2022.109323. Epub 2022 Jun 14.
The identification of new diagnostic and therapeutic biomarkers might be helpful to understand molecular mechanism of cancer pathogenesis and develop anti-cancer targets. This study reported the alteration of Sodium channel 1 subunit alpha (SCNN1A) expression, its prognostic significance and biological roles in pancreatic cancer. Bioinformatics database was searched to explore the expression of SCNN1A in pancreatic cancer specimens and analysis results were further validated by qRT-PCR and Western blot assay. The correlation between SCNN1A expression and clinicopathological characteristics and its impact on survival outcome of pancreatic cancer patients were investigated using GEPIA database and Kaplan-Meier plotter. Loss- and gain-of-functional experiments in vitro were done to investigate the biological function of SCNN1A in pancreatic cancer. Bioinformatics analysis and validation experiment showed that SCNN1A was frequently overexpressed in pancreatic cancer specimens and cell lines (P < 0.001), and there were significant relevance between high SCNN1A expression and TP53 mutation (P < 0.05) as well as unfavorable prognosis of pancreatic cancer patients (HR for overall survival: 1.9, P = 0.003 and HR for disease-free survival: 1.7, P = 0.014). The silencing of SCNN1A suppressed cell proliferation, migration and invasion and induced cell apoptosis (P < 0.05), while its overexpression promoted aggressive phenotypes of pancreatic cancer cells in vitro (P < 0.05). SCNN1A possessed oncogenic function and its dysregulation could be implicated in the development and metastasis of pancreatic cancer.
新的诊断和治疗生物标志物的鉴定可能有助于了解癌症发病机制的分子机制，并开发抗癌靶点。本研究报告了钠离子通道 1 亚基 α（SCNN1A）表达的改变，及其在胰腺癌中的预后意义和生物学作用。通过生物信息学数据库搜索，探讨 SCNN1A 在胰腺癌标本中的表达，并用 qRT-PCR 和 Western blot 检测分析结果进行验证。利用 GEPIA 数据库和 Kaplan-Meier plotter 分析 SCNN1A 表达与临床病理特征的相关性及其对胰腺癌患者生存结局的影响。通过体外的缺失和功能获得实验，研究 SCNN1A 在胰腺癌中的生物学功能。生物信息学分析和验证实验表明，SCNN1A 在胰腺癌标本和细胞系中频繁过表达（P<0.001），并且高 SCNN1A 表达与 TP53 突变（P<0.05）以及胰腺癌患者不良预后有显著相关性（总生存的 HR：1.9，P=0.003；无病生存的 HR：1.7，P=0.014）。SCNN1A 的沉默抑制了细胞增殖、迁移和侵袭，并诱导了细胞凋亡（P<0.05），而其过表达则促进了胰腺癌细胞在体外的侵袭表型（P<0.05）。SCNN1A 具有致癌功能，其失调可能与胰腺癌的发生和转移有关。
