title: OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway.
abstract: Orthodenticlehomeobox 1 (OTX1) overexpression had previously been associated with the progression of several tumors. The present study aimed to determine the expression and role of OTX1 in human hepatocellular carcinoma (HCC). The expression level of OTX1 was examined by quantitative real-time PCR (qRT-PCR) in 10 samples of HCC and paired adjacent non-cancerous tissues, and by immunohistochemistry (IHC) analysis in 128 HCC samples and matched controls. The relationship between OTX1 expression and the clinicopathological features werealso analyzed. Furthermore, the effects of OTX1 knockdown on cell proliferation and migration were determined in HCC cell lines. Axenograft mouse model was also established to investigate the role of OTX1 in HCC tumor growth. TheqRT-PCR and IHC analyses revealed that OTX1 was significantly elevated in HCC tissues compared with the paired non-cancerous controls. Expression of OTX1 was positively correlated with nodal metastasis status (P = 0.009) and TNM staging (P = 0.001) in HCC tissues. In addition, knockdown of OTX1 by shRNA significantly inhibited the proliferation and migration, and induced cell cycle arrest in S phase in vitro. Tumor growth was markedly inhibited by OTX1 silencing in the xenograft. Moreover, OTX1 silencing was causable for the decreased phosphorylation level of ERK/MAPK signaling. In conclusion, OTX1 contributes to HCC progression possibly by regulation of ERK/MAPK pathway. OTX1 may be a novel target for molecular therapy towards HCC.
authors.affiliation: Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China .
authors.forename: Hua
authors.identifier: 0000-0003-1728-1622
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oncology, Quzhou People's Hospital in Zhejiang Province, Quzhou Zhejiang, China .
authors.forename: Qian
authors.identifier: 0000-0002-1864-5697
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Department of Pathology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China .
authors.forename: Chun-Wei
authors.identifier: 0000-0002-9021-6731
authors.initials: CW
authors.lastname: Xu
authors.affiliation: Department of Oncology, Lishui Central Hospital, Lishui Hospital of Zhejiang University, Lishui, Zhejiang, China .
authors.forename: Jian-Hui
authors.identifier: 0000-0002-2854-112X
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Department of Oncology, Lishui Central Hospital, Lishui Hospital of Zhejiang University, Lishui, Zhejiang, China .
authors.forename: Yue-Fen
authors.identifier: 0000-0002-0872-9782
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Zhejiang, China .
authors.forename: Mei-Juan
authors.identifier: 0000-0001-7893-2287
authors.initials: MJ
authors.lastname: Wu
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D051857:Otx Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D059807:S Phase Cell Cycle Checkpoints; D014183:Transplantation, Heterologous
chemical_list: C497655:OTX1 protein, human; D051857:Otx Transcription Factors
keywords: ERK/MAPK; Growth; Hepatocellular Carcinoma; Migration; OTX1