DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes

Autor:	Masashi Idogawa, Eiichiro Yamamoto, Yui Hatanaka, M Toyota, Kazuhiro Ogi, Takashi Tokino, Masahiro Kai, Koyo Nishiyama, Takeshi Niinuma, Reo Maruyama, Hironari Dehari, Akihiro Miyazaki, Yasushi Sasaki, Hiromu Suzuki, Hiroshi Kitajima, Shohei Sekiguchi, Akira Yorozu, Kazuya Ishiguro
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Science Biology Article Western blot Interferon Cell Line Tumor medicine Humans Phosphorylation Head and neck cancer Receptors Interferon Gene knockdown Multidisciplinary medicine.diagnostic_test Cell growth Oral cancer Oncogenes medicine.disease Antigens Differentiation Up-Regulation Chromatin Gene Expression Regulation Neoplastic Histone Code Leukemia stomatognathic diseases STAT1 Transcription Factor Acetylation Carcinoma Squamous Cell Long non-coding RNAs Cancer research H3K4me3 Medicine Mouth Neoplasms RNA Long Noncoding Interferons Genes Neoplasm medicine.drug
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Scientific Reports
ISSN:	2045-2322
Popis:	Long noncoding RNAs (lncRNAs) are deeply involved in cancer development. We previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is one of the lncRNAs overexpressed in oral squamous cell carcinoma (OSCC) cells, where it exhibits oncogenic activity. In the present study, we further clarified the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that DLEU1 knockdown induced significant changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, DLEU1 knockdown suppressed levels of H3K4me3/ H3K27ac and expression of a number of interferon-stimulated genes (ISGs), including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assays suggested that DLEU1 upregulates ISGs through activation of JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, was frequently overexpressed in primary OSCC tumors, and its knockdown inhibited OSCC cell proliferation, migration and invasion. These findings suggest that DLEU1 exerts its oncogenic effects, at least in part, through activation of a series ISGs in OSCC cells.
Databáze:	OpenAIRE
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