OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway.
OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway.
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DOI：
10.3346/jkms.2016.31.8.1215
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发表时间：
2016-08
影响因子：
4.5
通讯作者：
Wu MJ
中科院分区：
文献类型：
--
作者：
Li H;Miao Q;Xu CW;Huang JH;Zhou YF;Wu MJ
正齿同源异型框1（OTX 1）过表达以前与几种肿瘤的进展有关。本研究旨在确定OTX 1在人肝细胞癌（HCC）中的表达和作用。采用实时荧光定量PCR（qRT-PCR）检测10例肝癌组织及配对癌旁组织中OTX 1的表达水平，采用免疫组化（IHC）检测128例肝癌组织及配对对照组织中OTX 1的表达水平。分析OTX 1表达与临床病理特征的关系。此外，在HCC细胞系中测定了OTX 1敲低对细胞增殖和迁移的影响。同时建立了小鼠肝移植瘤模型，研究OTX 1在肝癌生长中的作用。qRT-PCR和IHC分析显示，与配对的非癌对照相比，OTX 1在HCC组织中显著升高。OTX 1的表达与HCC组织的淋巴结转移（P = 0.009）和TNM分期（P = 0.001）呈正相关。此外，OTX 1基因在体外可显著抑制细胞的增殖和迁移，并使细胞周期阻滞于S期。肿瘤生长在异种移植物中被OTX 1沉默显著抑制。此外，OTX 1沉默可导致ERK/MAPK信号的磷酸化水平降低。总之，OTX 1可能通过调节ERK/MAPK通路促进HCC进展。OTX 1可能成为肝癌分子治疗的新靶点。
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.