RRC ID 41310
Author Nishizawa Y, Nishida N, Konno M, Kawamoto K, Asai A, Koseki J, Takahashi H, Haraguchi N, Nishimura J, Hata T, Matsuda C, Mizushima T, Satoh T, Doki Y, Mori M, Ishii H.
Title Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer.
Journal Ann Surg Oncol
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.
Volume 24(3)
Pages 841-849
Published 2017-3-1
DOI 10.1245/s10434-016-5395-9
PII 10.1245/s10434-016-5395-9
PMID 27473587
MeSH Apoptosis / genetics Biomarkers, Tumor / metabolism Blood Vessels / pathology Cell Movement / genetics Cell Proliferation / genetics Chromosomal Proteins, Non-Histone / genetics* Chromosomal Proteins, Non-Histone / metabolism* Colorectal Neoplasms / metabolism* Colorectal Neoplasms / pathology* Dioxygenases Disease-Free Survival Female G1 Phase Cell Cycle Checkpoints / genetics Gene Expression Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HCT116 Cells HT29 Cells Histone Demethylases / genetics* Histone Demethylases / metabolism* Humans Immunohistochemistry Lymphatic Metastasis Lymphatic Vessels / pathology Male Neoplasm Invasiveness Neoplasm Staging Proto-Oncogene Proteins c-myc / genetics RNA, Small Interfering Survival Rate Transfection
IF 4.061
Times Cited 8
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385)