Xu Ruirui, Xu Mingyan, Fu Yucai, Deng Xiaoling, Han Hui, Chen Xihe, He Wenjing, Chen Gengzhen
Minimally Invasive Medical Center, The Second Affiliated Hospital of Shantou Medical College, Shantou, Guangdong 515041, P.R. China.
Laboratory of Cell Senescence, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
Oncol Lett. 2018 Jul;16(1):439-446. doi: 10.3892/ol.2018.8672. Epub 2018 May 8.
Although it is difficult to detect αvβ6 integrin (αvβ6) in normal epithelia cells, its expression is upregulated during wound healing and carcinogenesis. Overexpression of αvβ6 has been demonstrated in epithelial cell carcinomas, such as adenocarcinoma of the colon and ovary. However, the expression of αvβ6 has not been reported in hepatocellular carcinoma (HCC). We previously indicated that LPA may induce αvβ6-mediated TGF-β1 signaling mechanisms during the pathogenesis of lung injury and fibrosis. In addition, transforming growth factor-β1 (TGF-β1) and lysophosphatidic acid (LPA) have been demonstrated to participate in the progression of HCC. In the present study, we hypothesized that TGF-β1 and LPA would serve a key role in the subunit integrin β6 (Itgβ6) transcriptional regulatory mechanism in HCC. It was identified that human HCC tissues and Hep-3B cells expressed Itgβ6. Treatment of Hep-3B with TGF-β1 or LPA increased the expression of Itgβ6. Furthermore, truncation experiments indicated a positive regulatory region at -326 to -157 bp of the Itgβ6 promoter. TGF-β1 and LPA increased transcriptional activation at this regulatory region. To the best of our knowledge, the present study was the first to demonstrate Itgβ6 expression in HCC, and the data indicate that TGF-β1 and LPA regulate Itgβ6 expression through the Itgβ6 gene promoter, which is an important factor in the development of HCC.
尽管在正常上皮细胞中很难检测到αvβ6整合素（αvβ6），但其表达在伤口愈合和癌变过程中上调。αvβ6的过表达已在诸如结肠癌和卵巢癌等上皮细胞癌中得到证实。然而，αvβ6在肝细胞癌（HCC）中的表达尚未见报道。我们先前指出，溶血磷脂酸（LPA）可能在肺损伤和纤维化的发病机制中诱导αvβ6介导的转化生长因子-β1（TGF-β1）信号传导机制。此外，已证实转化生长因子-β1（TGF-β1）和溶血磷脂酸（LPA）参与HCC的进展。在本研究中，我们假设TGF-β1和LPA在HCC的亚基整合素β6（Itgβ6）转录调节机制中起关键作用。已确定人HCC组织和Hep-3B细胞表达Itgβ6。用TGF-β1或LPA处理Hep-3B可增加Itgβ6的表达。此外，截短实验表明在Itgβ6启动子的-326至-157 bp处存在一个正调控区域。TGF-β1和LPA增加了该调控区域的转录激活。据我们所知，本研究首次证明了Itgβ6在HCC中的表达，并且数据表明TGF-β1和LPA通过Itgβ6基因启动子调节Itgβ6的表达，这是HCC发生发展中的一个重要因素。
