Long non-coding RNA highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma

J Cell Mol Med. 2019 Apr;23(4):2645-2655. doi: 10.1111/jcmm.14160. Epub 2019 Jan 24.

Abstract

Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy that exhibits high incidence worldwide. In diverse human cancers, the long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) is aberrantly expressed, but how HULC affects OSCC development and progression has remained mostly unknown. We report that HULC was abnormally up-regulated in oral cancer tissues and OSCC cell lines, and that suppression of HULC expression in OSCC cells not only inhibited the proliferation, drug tolerance, migration and invasion of the cancer cells, but also increased their apoptosis rate. Notably, in a mouse xenograft model, HULC depletion reduced tumorigenicity and inhibited the epithelial-to-mesenchymal transition process. Collectively, our findings reveal a crucial role of the lncRNA HULC in regulating oral cancer carcinogenesis and tumour progression, and thus suggest that HULC could serve as a novel therapeutic target for OSCC.

Keywords: epithelial-to-mesenchymal transition; highly up-regulated in liver cancer; long non-coding RNA; oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Tumor Burden
  • Vimentin / genetics
  • Vimentin / metabolism
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antigens, CD
  • BAX protein, human
  • BCL2 protein, human
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • HULC long non-coding RNA, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • VIM protein, human
  • Vimentin
  • bcl-2-Associated X Protein