title: Identification of the involvement of LOXL4 in generation of keratocystic odontogenic tumors by RNA-Seq analysis.
abstract: Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density (MVD) than dentigerous cysts (DC) and normal oral mucosa. To identify genes in the stroma of KCOT involved in tumor development and progression, RNA sequencing (RNA-Seq) was performed using samples from KCOT and primary stromal fibroblasts isolated from gingival tissues. Seven candidate genes that possess a function potentially related to KCOT progression were selected and their expression levels were confirmed by quantitative PCR, immunohistochemistry and enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 (LOXL4), the only candidate gene that encodes a secreted protein, was enhanced at both the mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal fibroblasts compared to control tissues and primary fibroblasts (P<0.05). In vitro, high expression of LOXL4 could enhance proliferation and migration of the human umbilical vein endothelial cells (HUVECs). There was a significant, positive correlation between LOXL4 protein expression and MVD in stroma of KCOT and control tissues (r=0.882). These data suggest that abnormal expression of LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the locally aggressive biological behavior of KCOT.
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Jiang
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Zi-Han
authors.initials: ZH
authors.lastname: Sima
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Hai-Cheng
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Jian-Yun
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: Sun
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Li
mesh_terms: D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003803:Dentigerous Cyst / Q000201:enzymology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005881:Gingiva / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics; D009808:Odontogenic Tumors / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D008249:Protein-Lysine 6-Oxidase; D017423:Sequence Analysis, RNA; D017154:Stromal Cells / Q000473:pathology; D055815:Young Adult
chemical_list: D000594:Amino Acid Oxidoreductases; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase