LncRNA MALAT1 promotes growth and metastasis of head and neck squamous cell carcinoma by repressing VHL through a non-canonical function of EZH2

Cell Death Dis. 2023 Feb 22;14(2):149. doi: 10.1038/s41419-023-05667-6.

Abstract

Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel-Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of β-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Enhancer of Zeste Homolog 2 Protein* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / genetics
  • Humans
  • NF-kappa B / genetics
  • RNA, Long Noncoding* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein* / genetics

Substances

  • Enhancer of Zeste Homolog 2 Protein
  • EZH2 protein, human
  • NF-kappa B
  • RNA, Long Noncoding
  • VHL protein, human
  • Von Hippel-Lindau Tumor Suppressor Protein
  • MALAT1 long non-coding RNA, human