TGF-β-induced STAT3 overexpression promotes human head and neck squamous cell carcinoma invasion and metastasis through malat1/miR-30a interactions.

Abstract

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is a critical factor that drives the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3 overexpression and regulation of HNSCC metastasis remain unknown. In the current study, we demonstrated that upregulated TGF-β may promote epithelial-mesenchymal transition (EMT) through STAT3 activation. In addition, we explored the contributions of STAT3 to HNSCC with a specific focus on its transcriptional regulation and its interaction with the long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (malat1). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that STAT3 could bind to the malat1 promoter region and transcriptionally activate malat1 expression; then, malat1 interacted reciprocally with miR-30a, inducing EMT and accelerating HNSCC metastasis. In summary, our discoveries illuminate how aberrant STAT3 activation confers an oncogenic function in HNSCC and therefore may provide a theoretical foundation for STAT3 as a therapeutic target in HNSCC.

• Authors: Yu Wang, Chuanqiang Wu, Chao Zhang, Zhaoqing Li, Tingting Zhu, Jinliang Chen, Yu Ren, Xudong Wang, Lun Zhang, Xuan Zhou
• Journal: Cancer letters (Cancer Lett) Vol. 436 Pg. 52-62 (11 01 2018) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 30118844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• MALAT1 long non-coding RNA, human
• MIRN30b microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• STAT3 Transcription Factor
• STAT3 protein, human
• Transforming Growth Factor beta

Topics

• Animals
• Carcinoma, Squamous Cell (drug therapy, genetics, metabolism)
• Cell Line
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Epistasis, Genetic
• Epithelial-Mesenchymal Transition (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• HEK293 Cells
• Head and Neck Neoplasms (drug therapy, genetics, metabolism)
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• RNA Interference
• RNA, Long Noncoding (genetics, metabolism)
• STAT3 Transcription Factor (genetics, metabolism)
• Transforming Growth Factor beta (pharmacology)
• Xenograft Model Antitumor Assays (methods)