PMID- 34650128
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20220126
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Oct 14
TI  - DLEU1 promotes oral squamous cell carcinoma progression by activating 
      interferon-stimulated genes.
PG  - 20438
LID - 10.1038/s41598-021-99736-5 [doi]
LID - 20438
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Hatanaka, Yui
AU  - Hatanaka Y
AD  - Department of Oral Surgery, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Niinuma, Takeshi
AU  - Niinuma T
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Kitajima, Hiroshi
AU  - Kitajima H
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Nishiyama, Koyo
AU  - Nishiyama K
AD  - Department of Oral Surgery, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Maruyama, Reo
AU  - Maruyama R
AD  - Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer 
      Research, Tokyo, Japan.
FAU - Ishiguro, Kazuya
AU  - Ishiguro K
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
AD  - Department of Gastroenterology and Hepatology, Sapporo Medical University School 
      of Medicine, Sapporo, Japan.
FAU - Toyota, Mutsumi
AU  - Toyota M
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Yamamoto, Eiichiro
AU  - Yamamoto E
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Kai, Masahiro
AU  - Kai M
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Yorozu, Akira
AU  - Yorozu A
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
AD  - Department of Otolaryngology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Sekiguchi, Shohei
AU  - Sekiguchi S
AD  - Department of Oral Surgery, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
FAU - Ogi, Kazuhiro
AU  - Ogi K
AD  - Department of Oral Surgery, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Dehari, Hironari
AU  - Dehari H
AD  - Department of Oral Surgery, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Idogawa, Masashi
AU  - Idogawa M
AD  - Department of Medical Genome Science, Research Institute for Frontier Medicine, 
      Sapporo Medical University School of Medicine, Sapporo, Japan.
FAU - Sasaki, Yasushi
AU  - Sasaki Y
AD  - Biology Division, Department of Liberal Arts and Sciences, Center for Medical 
      Education, Sapporo Medical University, Sapporo, Japan.
FAU - Tokino, Takashi
AU  - Tokino T
AD  - Department of Medical Genome Science, Research Institute for Frontier Medicine, 
      Sapporo Medical University School of Medicine, Sapporo, Japan.
FAU - Miyazaki, Akihiro
AU  - Miyazaki A
AD  - Department of Oral Surgery, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Suzuki, Hiromu
AU  - Suzuki H
AD  - Department of Molecular Biology, Sapporo Medical University School of Medicine, 
      S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. hsuzuki@sapmed.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211014
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antigens, Differentiation)
RN  - 0 (DLEU1 lncRNA, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Receptors, Interferon)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (leu-13 antigen)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Antigens, Differentiation/metabolism
MH  - Carcinoma, Squamous Cell/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, Neoplasm
MH  - Histone Code
MH  - Humans
MH  - Interferons/metabolism
MH  - Mouth Neoplasms/metabolism/*pathology
MH  - Phosphorylation
MH  - RNA, Long Noncoding/*metabolism/physiology
MH  - Receptors, Interferon/metabolism
MH  - STAT1 Transcription Factor/metabolism
MH  - Up-Regulation
PMC - PMC8516910
COIS- The authors declare no competing interests.
EDAT- 2021/10/16 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/10/14
CRDT- 2021/10/15 06:06
PHST- 2021/07/13 00:00 [received]
PHST- 2021/09/30 00:00 [accepted]
PHST- 2021/10/15 06:06 [entrez]
PHST- 2021/10/16 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/10/14 00:00 [pmc-release]
AID - 10.1038/s41598-021-99736-5 [pii]
AID - 99736 [pii]
AID - 10.1038/s41598-021-99736-5 [doi]
PST - epublish
SO  - Sci Rep. 2021 Oct 14;11(1):20438. doi: 10.1038/s41598-021-99736-5.