Pancreatic cancer (PC) is a malignant tumor disease, whose molecular mechanism is not fully understood. Sodium channel epithelial 1α subunit (SCNN1A) serves an important role in tumor progression. The current study explored the role of homeobox D9 (HOXD9) and SCNN1A in the progression of PC. The expression of SCNN1A and HOXD9 in PC samples was predicted on online databases and detected in PC cell lines. The association between SCNN1A expression and PC prognosis was examined by the Gene Expression Profiling Interactive Analysis, The Cancer Genome Atlas and Genotype‑Tissue Expression databases and by a Kaplan‑Meier plotter. Subsequently, the biological effects of SCNN1A on PC cell growth, colony formation, migration and invasion were investigated through RNA interference and cell transfection. Next, the expression of E‑cadherin, N‑cadherin, Vimentin and Snail was detected by western blotting to discover whether HOXD9 dysregulation mediated PC metastasis. Binding sites of HOXD9 and SCNN1A promoters were predicted on JASPAR. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression level of SCNN1A following interference and overexpression of HOXD9. Luciferase assay detected luciferase activity following interference with HOXD9 and the transcriptional activity of SCNN1A following binding site deletion. High expression of SCNN1A and HOXD9 in PC was predicted by online databases, signifying poor prognosis. The present study confirmed the above predictions in PC cell lines. Knockdown of SCNN1A and HOXD9 could effectively inhibit the proliferation, migration, invasion and epithelial‑mesenchymal transition of PC cells. Furthermore, HOXD9 activated SCNN1A transcription, forming a feedback regulatory loop. HOXD9 was demonstrated to activate SCNN1A and promote the malignant biological process of PC.

中文翻译：

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HOXD9 诱导的 SCNN1A 上调通过调节上皮间质转化促进胰腺癌细胞增殖、迁移并预测预后。

胰腺癌（PC）是一种恶性肿瘤疾病，其分子机制尚不完全清楚。钠通道上皮 1α 亚基 (SCNN1A) 在肿瘤进展中起重要作用。目前的研究探讨了同源框 D9 (HOXD9) 和 SCNN1A 在 PC 进展中的作用。在在线数据库上预测 PC 样本中 SCNN1A 和 HOXD9 的表达，并在 PC 细胞系中检测到。通过基因表达谱交互分析、癌症基因组图谱和基因型组织表达数据库以及 Kaplan-Meier 绘图仪检查了 SCNN1A 表达与 PC 预后之间的关联。随后，通过RNA干扰和细胞转染研究了SCNN1A对PC细胞生长、集落形成、迁移和侵袭的生物学作用。接下来，E-cadherin、N-cadherin 的表达，通过蛋白质印迹检测波形蛋白和蜗牛，以发现 HOXD9 失调是否介导 PC 转移。在 JASPAR 上预测了 HOXD9 和 SCNN1A 启动子的结合位点。逆转录定量 PCR 和蛋白质印迹用于检测 HOXD9 干扰和过表达后 SCNN1A 的表达水平。荧光素酶测定检测到干扰 HOXD9 后的荧光素酶活性和结合位点缺失后 SCNN1A 的转录活性。在线数据库预测 SCNN1A 和 HOXD9 在 PC 中的高表达，表明预后不良。本研究证实了 PC 细胞系中的上述预测。敲低 SCNN1A 和 HOXD9 可有效抑制 PC 细胞的增殖、迁移、侵袭和上皮间质转化。此外，HOXD9 激活 SCNN1A 转录，形成反馈调节环。HOXD9 被证明可激活 SCNN1A 并促进 PC 的恶性生物学过程。