PMID- 30069008 OWN - NLM STAT- MEDLINE DCOM- 20191203 LR - 20220409 IS - 2041-4889 (Electronic) VI - 9 IP - 8 DP - 2018 Aug 1 TI - Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1. PG - 826 LID - 10.1038/s41419-018-0893-2 [doi] LID - 826 AB - Recent studies have shown that long noncoding RNAs (lncRNAs) have pivotal roles in human malignancies, although their significance in oral squamous cell carcinoma (OSCC) is not fully understood. In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC), we identified 15 lncRNAs aberrantly expressed in cancer tissues. We then validated their expression in 18 OSCC cell lines using qRT-PCR and identified 6 lncRNAs frequently overexpressed in OSCC. Among those, we found that knocking down DLEU1 (deleted in lymphocytic leukemia 1) strongly suppressed OSCC cell proliferation. DLEU1 knockdown also suppressed migration, invasion, and xenograft formation by OSCC cells, which is suggestive of its oncogenic functionality. Microarray analysis revealed that DLEU1 knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44, and TP63, suggesting that DLEU1 regulates HA-CD44 signaling. Expression of DLEU1 was elevated in 71% of primary OSCC tissues, and high DLEU1 expression was associated with shorter overall survival of HNSCC patients. These data suggest that elevated DLEU1 expression contributes to OSCC development, and that DLEU1 may be a useful therapeutic target in OSCC. FAU - Nishiyama, Koyo AU - Nishiyama K AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. AD - Department of Molecular Biology, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. FAU - Maruyama, Reo AU - Maruyama R AD - Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, 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 - 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 - 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 - 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 - Hatanaka, Yui AU - Hatanaka Y AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. AD - Department of Molecular Biology, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. FAU - Igarashi, Tomohiro AU - Igarashi T AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. FAU - Kobayashi, Jun-Ichi AU - Kobayashi JI AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. FAU - Ogi, Kazuhiro AU - Ogi K AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. FAU - Dehari, Hironari AU - Dehari H AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. FAU - Miyazaki, Akihiro AU - Miyazaki A AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, 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. 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 - Idogawa, Masashi AU - Idogawa M AUID- ORCID: 0000-0002-8507-1726 AD - Department of Medical Genome Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. FAU - Sasaki, Yasushi AU - Sasaki Y AD - Department of Medical Genome Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. FAU - Sugai, Tamotsu AU - Sugai T AD - Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan. FAU - Tokino, Takashi AU - Tokino T AD - Department of Medical Genome Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. FAU - Hiratsuka, Hiroyoshi AU - Hiratsuka H AD - Department of Oral Surgery, Sapporo Medical University School of Medicine, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan. FAU - Suzuki, Hiromu AU - Suzuki H AUID- ORCID: 0000-0001-9635-3238 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 - 20180801 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (DLEU1 lncRNA, human) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/metabolism/mortality/*pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Kaplan-Meier Estimate MH - Mice MH - Mice, Nude MH - Mouth Neoplasms/metabolism/mortality/*pathology MH - RNA Interference MH - RNA, Long Noncoding/antagonists & inhibitors/genetics/*metabolism MH - RNA, Small Interfering/metabolism MH - Tumor Suppressor Proteins/antagonists & inhibitors/genetics/*metabolism PMC - PMC6070574 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/08/03 06:00 MHDA- 2019/12/04 06:00 PMCR- 2018/08/01 CRDT- 2018/08/03 06:00 PHST- 2018/03/02 00:00 [received] PHST- 2018/07/18 00:00 [accepted] PHST- 2018/07/18 00:00 [revised] PHST- 2018/08/03 06:00 [entrez] PHST- 2018/08/03 06:00 [pubmed] PHST- 2019/12/04 06:00 [medline] PHST- 2018/08/01 00:00 [pmc-release] AID - 10.1038/s41419-018-0893-2 [pii] AID - 893 [pii] AID - 10.1038/s41419-018-0893-2 [doi] PST - epublish SO - Cell Death Dis. 2018 Aug 1;9(8):826. doi: 10.1038/s41419-018-0893-2.