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Background: Transmembrane-4-L-six-family-1 (TM4SF1) functions to regulate cell growth and mobility and TM4SF1 expression was upregulated in pancreatic cancer. This study further investigated the role of TM4SF1 in regulating pancreatic cancer epithelial-mesenchymal transition (EMT) and angiogenesis and the underlying molecular events. Methods: Tissue specimens were collected from 90 pancreatic cancer patients for immunohistochemical and qRT-PCR analysis of miR-141 and TM4SF1 levels, respectively. Pancreatic cancer cell lines were used for in vitro assays, while nude mice were used for the in vivo assay. Results: TM4SF1 expression was upregulated, whereas miR-141 expression was lost in pancreatic cancer tissues, both of which was associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Furthermore, miR-141 was able to target and reduce TM4SF1 expression in pancreatic cancer cells and miR-141 expression inhibited pancreatic cancer cell EMT in vitro and Matrigel plug angiogenesis and lung metastasis in nude mice. At the gene level, miR-141 directly targeted and reduced TM4SF1 expression and in turn induced E-cadherin expression and reduced VEGF-A expression by suppressing activation of the AKT signaling pathway. Conclusions: This study demonstrated that upregulated TM4SF1 and lost miR-141 expression were associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Lost miR-141 expression but induced TM4SF1 expression altered expression of VEGF-A and E-cadherin and promoted pancreatic cancer cell EMT and angiogenesis via the AKT signaling pathway, suggesting that targeting of miR-141 and TM4SF1 may be a potential therapeutic strategy to control pancreatic cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly malignant neoplastic disease of the digestive system. In the present study, the dataset GSE62165 was downloaded from the Gene Expression Omnibus (GEO) database. GSE62165 contained the data of 118 pancreatic ductal adenocarcinoma samples (38 early-stage tumors, 62 lymph node metastases and 18 advanced tumors) and 13 control samples. Differences in the expression levels of genes between normal tissues and early-stage tumors were investigated. A total of 240 differentially expressed genes (DEGs) were identified using R software 3.5 (137 upregulated genes and 103 downregulated genes). Then, the differentially expressed genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The following 18 core genes were identified using Cytoscape, based on the protein-interaction network of DEGs determined using the online tool STRING: EGF, ALB, COL17A1, FN1, TIMP1, PLAU, PLA2G1B, IGFBP3, PLAUR, VCAN, COL1A1, PNLIP, CTRL, PRSS3, COMP, CPB1, ITGA2 and CEL. The pathways of the core genes were primarily associated with pancreatic secretion, protein digestion and absorption, and focal adhesion. Finally, survival analyses of core genes in pancreatic cancer were conducted using the UALCAN online database. It was revealed that PLAU and COL17A1 were significantly associated with poor prognosis (P<0.05). The expression levels of genes in primary pancreatic cancer tissues were then compared; only one gene, COL17A1, was identified to be significantly differentially expressed. Finally, another dataset from GEO, GSE28735, was analyzed to verify the upregulated expression of COL17A1. Taken together, the results of the present study have indicated that the expression of COL17A1 gene may be associated with the occurrence and development of pancreatic cancer. [ABSTRACT FROM AUTHOR]