Wang Yazhou, Guo Huahu, Zhang Dafang, Yu Xin, Leng Xisheng, Li Shu, Zhu Weihua
Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People's Hospital, Beijing, 100044, China.
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China.
Biochem Biophys Res Commun. 2016 Oct 21;479(3):510-516. doi: 10.1016/j.bbrc.2016.09.099. Epub 2016 Sep 20.
Transcription factor SOX18 has been proved to play a significant role in carcinogenesis. However, no investigation was performed about the expression of SOX18 in pancreatic ductal adenocarcinoma (PDAC). In our work, we found that the PDAC tissues had higher level of SOX18 mRNA and protein expression than matched non-tumor pancreatic tissues and high level of SOX18 protein indicated poor prognosis for PDAC patients. After knockdown of SOX18 gene in PANC-1 and SW1990 cell lines, which showed higher expression level of SOX18 among five PDAC cell lines, the abilities of proliferation, migration and invasion were inhibited and the tumor growth was suppressed in vivo. In addition, the flow cytometry results indicated that down-regulation of SOX18 induced G1/S phase arrest. Furthermore, we found that the expression of cyclin D1, c-myc and MMP-7, three tumorigenesis promoters, was inhabited with downregulation of SOX18. In conclusion, our study reveals that SOX18 plays a significant role in promoting the growth of PDAC, and might serve as a promising target for PDAC therapy.
转录因子SOX18已被证明在肿瘤发生中起重要作用。然而,尚未对SOX18在胰腺导管腺癌(PDAC)中的表达进行研究。在我们的研究中,我们发现PDAC组织中SOX18 mRNA和蛋白表达水平高于配对的非肿瘤胰腺组织,且SOX18蛋白水平高表明PDAC患者预后不良。在PANC-1和SW1990细胞系(在五种PDAC细胞系中SOX18表达水平较高)中敲低SOX18基因后,其增殖、迁移和侵袭能力受到抑制,体内肿瘤生长也受到抑制。此外,流式细胞术结果表明,SOX18的下调诱导G1/S期阻滞。此外,我们发现细胞周期蛋白D1、c-myc和MMP-7这三种肿瘤发生促进因子的表达随着SOX18的下调而受到抑制。总之,我们的研究表明SOX18在促进PDAC生长中起重要作用,可能是PDAC治疗的一个有前景的靶点。