OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway

Autor: Qian Miao, Hua Li, Chun Wei Xu, Jian Hui Huang, Yue Fen Zhou, Mei Juan Wu
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
MAPK/ERK pathway
Male
Cell cycle checkpoint
Growth
Small hairpin RNA
Mice
0302 clinical medicine
Cell Movement
Phosphorylation
Migration
Gene knockdown
Mice
Inbred BALB C
Otx Transcription Factors
Liver Neoplasms
General Medicine
Middle Aged
Immunohistochemistry
Gene Expression Regulation
Neoplastic
Liver
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Lymphatic Metastasis
S Phase Cell Cycle Checkpoints
Disease Progression
Original Article
Female
RNA Interference
Carcinoma
Hepatocellular
MAP Kinase Signaling System
Blotting
Western
Transplantation
Heterologous
Mice
Nude
Biology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Cell Line
Tumor
medicine
Gene silencing
Animals
Humans
Oncology & Hematology
ERK/MAPK
Aged
Cell Proliferation
Neoplasm Staging
Cell growth
Hepatocellular Carcinoma
medicine.disease
digestive system diseases
OTX1
030104 developmental biology
Cancer research
Zdroj: Journal of Korean Medical Science
ISSN: 1598-6357
1011-8934
Popis: 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.
Databáze: OpenAIRE
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