HOXD9‑induced SCNN1A upregulation promotes pancreatic cancer cell proliferation, migration and predicts prognosis by regulating epithelial‑mesenchymal transformation

Chang,Jinhai; Hu,Xuguang; Nan,Jinniang; Zhang,Xianghua; Jin,Xintian

doi:10.3892/mmr.2021.12459

HOXD9‑induced SCNN1A upregulation promotes pancreatic cancer cell proliferation, migration and predicts prognosis by regulating epithelial‑mesenchymal transformation

Authors:
- Jinhai Chang
- Xuguang Hu
- Jinniang Nan
- Xianghua Zhang
- Xintian Jin
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Affiliations: Department of Internal Medicine, Yanbian Hospital of Traditional Chinese Medicine, Yanbian, Jilin 133000, P.R. China, Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China, Department of Clinical Medicine, Jiangxi Health Vocational College of China, Nanchang, Jiangxi 330052, P.R. China, Department of Thoracic Oncology, Jilin Province Cancer Hospital, Changchun, Jilin 130000, P.R. China, Department of Thoracic Surgery, Jilin Province Cancer Hospital, Changchun, Jilin 130000, P.R. China
Published online on: September 22, 2021 https://doi.org/10.3892/mmr.2021.12459
Article Number: 819
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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