OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway.
10.3346/jkms.2016.31.8.1215
- Author:
Hua LI
1
;
Qian MIAO
;
Chun Wei XU
;
Jian Hui HUANG
;
Yue Fen ZHOU
;
Mei Juan WU
Author Information
1. Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.
- Publication Type:Original Article
- Keywords:
OTX1;
Hepatocellular Carcinoma;
Growth;
Migration;
ERK/MAPK
- MeSH:
Aged;
Animals;
Blotting, Western;
Carcinoma, Hepatocellular/metabolism/*pathology;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Disease Progression;
Female;
Gene Expression Regulation, Neoplastic;
Humans;
Immunohistochemistry;
Liver/metabolism/pathology;
Liver Neoplasms/metabolism/*pathology;
Lymphatic Metastasis;
MAP Kinase Signaling System;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Middle Aged;
Neoplasm Staging;
Otx Transcription Factors/antagonists & inhibitors/genetics/*metabolism;
Phosphorylation;
RNA Interference;
Real-Time Polymerase Chain Reaction;
S Phase Cell Cycle Checkpoints;
Transplantation, Heterologous
- From:Journal of Korean Medical Science
2016;31(8):1215-1223
- CountryRepublic of Korea
- Language:English
-
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.
