Yujiro Nishizawa1, Naohiro Nishida2, Masamitsu Konno2, Koichi Kawamoto1, Ayumu Asai3, Jun Koseki3, Hidekazu Takahashi1, Naotsugu Haraguchi1, Junichi Nishimura1, Taishi Hata1, Chu Matsuda1, Tsunekazu Mizushima1, Taroh Satoh2, Yuichiro Doki1, Masaki Mori4, Hideshi Ishii5,6. 1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 2. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 3. Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 4. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. mmori@gesurg.med.osaka-u.ac.jp. 5. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hishii@gesurg.med.osaka-u.ac.jp. 6. Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hishii@gesurg.med.osaka-u.ac.jp.
Abstract
BACKGROUND: Targeting epigenetic regulators is a promising therapeutic strategy against cancer. However, because of the broad spectrum of targets, selective inhibition of cancer-associated genes remains a major challenge. To address this issue, we focused on the oncogene-regulated histone demethylase, nucleolar protein 66 (NO66 [C14orf169/MAPJD]), which is known to work coordinately with the well-characterized oncogene, c-MYC. METHODS: To investigate expression patterns and clinical significance of NO66 in colorectal cancer (CRC), we performed immunohistochemical staining in 114 CRC cases. We performed functional analysis of NO66 to evaluate its contribution to proliferation and migration ability in CRC cells in vitro. RESULTS: NO66 was selectively expressed in CRC tissues. Furthermore, high expression levels of NO66 were associated with cancer metastatic potential, including lymphatic duct invasion (p = 0.047), venous invasion (p = 0.033), and lymph node metastasis (p = 0.015). Multivariate analysis indicated that NO66 was an independent prognostic factor for overall survival. In vitro assays revealed that NO66 expression is closely associated with malignant potential, including proliferation, migration and anti-apoptotic activity. CONCLUSIONS: NO66 is an independent prognostic factor in CRC. The cancer-selective expression patterns and its involvement in metastatic phenotypes suggest that NO66 is not only a crucial biomarker but is also a promising therapeutic target in CRC.
BACKGROUND: Targeting epigenetic regulators is a promising therapeutic strategy against cancer. However, because of the broad spectrum of targets, selective inhibition of cancer-associated genes remains a major challenge. To address this issue, we focused on the oncogene-regulated histone demethylase, nucleolar protein 66 (NO66 [C14orf169/MAPJD]), which is known to work coordinately with the well-characterized oncogene, c-MYC. METHODS: To investigate expression patterns and clinical significance of NO66 in colorectal cancer (CRC), we performed immunohistochemical staining in 114 CRC cases. We performed functional analysis of NO66 to evaluate its contribution to proliferation and migration ability in CRC cells in vitro. RESULTS:NO66 was selectively expressed in CRC tissues. Furthermore, high expression levels of NO66 were associated with cancer metastatic potential, including lymphatic duct invasion (p = 0.047), venous invasion (p = 0.033), and lymph node metastasis (p = 0.015). Multivariate analysis indicated that NO66 was an independent prognostic factor for overall survival. In vitro assays revealed that NO66 expression is closely associated with malignant potential, including proliferation, migration and anti-apoptotic activity. CONCLUSIONS:NO66 is an independent prognostic factor in CRC. The cancer-selective expression patterns and its involvement in metastatic phenotypes suggest that NO66 is not only a crucial biomarker but is also a promising therapeutic target in CRC.
Authors: Katharina E Bräuer; Kevin Brockers; Jasmin Moneer; Annette Feuchtinger; Evi Wollscheid-Lengeling; Andreas Lengeling; Alexander Wolf Journal: BMC Evol Biol Date: 2018-06-19 Impact factor: 3.260