Identification of the involvement of LOXL4 in generation of keratocystic odontogenic tumors by RNA-Seq analysis.
- Author:
Wei-Peng JIANG
1
;
Zi-Han SIMA
1
;
Hai-Cheng WANG
1
;
Jian-Yun ZHANG
1
;
Li-Sha SUN
2
;
Feng CHEN
2
;
Tie-Jun LI
1
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Amino Acid Oxidoreductases; genetics; Cell Movement; genetics; Cell Proliferation; Dentigerous Cyst; enzymology; pathology; Disease Progression; Female; Fibroblasts; pathology; Gene Expression Regulation, Enzymologic; genetics; Gingiva; pathology; Human Umbilical Vein Endothelial Cells; pathology; Humans; Male; Microvessels; pathology; Neovascularization, Pathologic; genetics; Odontogenic Tumors; blood supply; enzymology; pathology; Sequence Analysis, RNA; Stromal Cells; pathology; Young Adult
- From: International Journal of Oral Science 2014;6(1):31-38
- CountryChina
- Language:English
- 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.
