Overexpression of ZEB2-AS1 promotes epithelial-to-mesenchymal transition and metastasis by stabilizing ZEB2 mRNA in head neck squamous cell carcinoma.

Abstract

The long noncoding RNAs (lncRNAs) have been increasingly appreciated as key players underlying tumourigenesis and hold great potentials as prognostic biomarkers and therapeutic targets. However, their roles in head neck squamous cell carcinoma (HNSCC) have remained incompletely known. Here, we sought to reveal the oncogenic roles and clinical significance of a tumour-associated lncRNA, zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), in HNSCC. ZEB2-AS1 was aberrantly overexpressed in a fraction of HNSCC samples. Its overexpression significantly associated with large tumour size, cervical node metastasis and reduced overall and disease-free survival. Antisense oligonucleotides (ASO)-mediated ZEB2-AS1 depletion markedly inhibited cell proliferation, migration and invasion while triggered apoptosis in HNSCC cells in part via modulating ZEB2 mRNA stability. Enforced overexpression of ZEB2 largely attenuated the phenotypic changes resulted from ZEB2-AS1 inhibition except the impaired cell proliferation. In addition, ZEB2-AS1 was required for TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro. Significantly reduced tumour growth and lung metastasis were observed in ZEB2-AS1-depleted cells in HNSCC xenograft animal models. Taken together, our findings reveal that overexpression of ZEB2-AS1 associates with tumour aggressiveness and unfavourable prognosis by serving as a putative oncogenic lncRNA and a novel prognostic biomarker in HNSCC.

• Authors: Pengfei Diao, Han Ge, Yue Song, Yaping Wu, Jin Li, Zhongwu Li, Jianrong Yang, Yanling Wang, Jie Cheng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 6 Pg. 4269-4280 (06 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 30950191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biomarkers, Tumor
• Oligonucleotides, Antisense
• RNA, Messenger
• ZEB2 protein, human
• Zinc Finger E-box Binding Homeobox 2

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Apoptosis
• Biomarkers, Tumor (genetics)
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Head and Neck Neoplasms (genetics, metabolism, pathology)
• Humans
• Male
• Mice
• Mice, Nude
• Middle Aged
• Oligonucleotides, Antisense (genetics, metabolism)
• Prognosis
• RNA Stability
• RNA, Messenger (chemistry, genetics, metabolism)
• Squamous Cell Carcinoma of Head and Neck (genetics, metabolism, secondary)
• Survival Rate
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Zinc Finger E-box Binding Homeobox 2 (antagonists & inhibitors, genetics)