LncNEN885 inhibits epithelial‐mesenchymal transition by partially regulation of Wnt/β‐catenin signalling in gastroenteropancreatic neuroendocrine neoplasms

• Published in: Cancer science 2018-10, Vol.109 (10), p.3139-3148
• Main Authors: Wei, Ya‐Ling, Hua, Jie, Liu, Xiao‐Yu, Hua, Xiu‐Mei, Sun, Cheng, Bai, Jian‐An, Tang, Qi‐Yun
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - genetics; beta Catenin - metabolism; Biomarkers; BON‐1 cell; Carcinogenesis; Catenin; Cell adhesion & migration; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Epithelial-Mesenchymal Transition - genetics; epithelial‐mesenchymal transition; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - pathology; Gastrointestinal Neoplasms - surgery; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Glycogen; Glycogen synthase kinase 3; Humans; Kinases; Liver cancer; lncNEN885; Medical prognosis; Mesenchyme; Metastases; Metastasis; Neoplasia; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; neuroendocrine neoplasm; Neuroendocrine tumors; Neuroendocrine Tumors - genetics; Neuroendocrine Tumors - pathology; Neuroendocrine Tumors - surgery; Original; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Phosphorylation; Polyposis coli; Proteins; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering; Stomach - pathology; Tumors; Vimentin; Wnt protein; Wnt Signaling Pathway - genetics; Wnt/β‐catenin signaling; Wound healing
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13747

It has been shown that long noncoding RNAs (lncRNAs) are involved in the carcinogenesis of multiple cancers. However, the roles of lncRNAs in gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) remain elusive. In the present study, we found that lncNEN885 was markedly decreased in human gastric NEN samples compared to adjacent normal tissues by transcriptome sequencing. Functionally, silencing or overexpression of lncNEN885 could not obviously affect cell proliferation or apoptosis in BON‐1 or LCC‐18 cells but could affect cell migration and invasion as well as wound‐healing rates. Furthermore, dysregulation of lncNEN885 affected these biological functions by activating epithelial‐mesenchymal transition through increased expression of Snail, vimentin, and N‐cadherin as well as decreased E‐cadherin levels in BON‐1 and LCC‐18 cells. Silencing of lncNEN885 could dramatically increase the phosphorylation of glycogen synthase kinase‐3β and decrease the expression of adenomatous polyposis coli and Axin, with the subsequent accumulation of β‐catenin. Taken together, dysregulation of lncNEN885 can regulate cell migration and invasion by activating epithelial‐mesenchymal transition process partially through canonical Wnt/β‐catenin signaling in GEP‐NEN cells, which may be a novel biomarker for the metastasis of GEP‐NENs. In our study, we found a novel lncRNA (Enst00000414885) named lncNEN885 in human gastric neuroendocrine neoplasms by transcriptome sequencing. LncNEN885 was markedly decreased in human gastric neuroendocrine neoplasm samples compared to adjacent normal tissues. Dysregulation of lncNEN885 could not obviously affect cellular proliferation or apoptosis but did influence cell migration, invasion, and wound‐healing rates in BON‐1 and LCC‐18 cells through activating epithelial‐mesenchymal transition partially through canonical Wnt/β‐catenin signaling. It is a potentially novel biomarker for the metastasis of gastroenteropancreatic neuroendocrine neoplasms.