title: UHRF1 expression is upregulated and associated with cellular proliferation             in colorectal cancer.
abstract: Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) binds to methylated             promoters of a number of tumor-suppressor genes, including p16INK4A and p14ARF,             by forming complexes with DNA methyltransferases and HDAC1, resulting in the induction             of carcinogenesis. Altered UHRF1 expression has been demonstrated in various types             of cancers. Previous reports indicate that UHRF1 expression is regulated by E2F-1             expression. We investigated UHRF1 expression using immunohistochemical staining             in 231 colorectal cancer and 40 adenoma specimens, analyzed the relationship between             UHRF1 expression and clinicopathological findings and the association between             UHRF1 and E2F-1 expression. To better understand the biological function of UHRF1             in colorectal cancer, knockdown of UHRF1 expression was performed using siRNA             methods. High UHRF1 expression was observed in 152 of 231 (65.8%) colorectal cancer             patients, and was detected in 35 of 40 adenoma specimens samples (87.5%). UHRF1             staining was detected in the nucleus of cancer cells, while it was not detected             in colonic normal mucosa. High UHRF1 expression was significantly observed in             right compared with left hemicolon cancer (p=0.008). Moreover, high UHRF1 expression             tended to be associated with depth of invasion (p=0.051). UHRF1 expression was             significantly associated with E2F-1 expression (p<0.0001). Knockdown of UHRF1             expression suppressed cellular growth in colon cancer cell lines, HCT116 and SW620.             In conclusion, we demonstrated that UHRF1 expression was upregulated in approximately             two-thirds of colorectal cancer specimens and was particularly expressed in right             compared with left hemicolon cancer. Moreover, knockdown of UHRF1 expression induced             growth inhibition in colon cancer cell lines. UHRF1 may be involved in cellular             proliferation and molecular pathogenesis of colorectal cancer in the right hemicolon.
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kofunato
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kumamoto
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Saitou
authors.forename: Suguru
authors.initials: S
authors.lastname: Hayase
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okayama
authors.forename: Kotaro
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Yu
authors.initials: Y
authors.lastname: Sato
authors.forename: Kyoko
authors.initials: K
authors.lastname: Katakura
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakamura
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.forename: Motoko
authors.initials: M
authors.lastname: Unoki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D034741:RNA, Small Interfering; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases