Satow Reiko, Aiga Yuna, Watanabe Takeru, Ishizuka Nako, Yoneda Atsuko, Fukami Kiyoko
Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Hachioji-shi, Tokyo, 192-0392, Japan.
Biochem Biophys Rep. 2022 Jun 2;31:101289. doi: 10.1016/j.bbrep.2022.101289. eCollection 2022 Sep.
Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are malignant tumors with poor prognosis because of the limited effectiveness of traditional chemotherapy and few effective molecular therapeutic agents. Here, we determined the essential roles of Zic family member 5 () in the survival of PDAC and CCA cells. The results showed that is strongly expressed in PDAC and CCA tissues, while expression is barely observed in most normal human adult tissues. Furthermore, expression is related to poor prognosis of patients with PDAC. knockdown via small interfering RNA decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3), a protein that is associated with PDAC and CCA aggressiveness. However, knockdown induced cell death regardless of STAT3 activation, which is promoted by interleukin (IL) -6, a factor associated with inflammation. Furthermore, knockdown of in PDAC and CCA cells additively or synergistically induced apoptosis with the anti-cancer drug gemcitabine. Thus, ZIC5 constitutes a potential therapeutic target for the treatment of PDAC and CCA.
胰腺导管腺癌（PDAC）和胆管癌（CCA）是预后较差的恶性肿瘤，因为传统化疗效果有限且有效的分子治疗药物很少。在此，我们确定了锌指蛋白家族成员5（ZIC5）在PDAC和CCA细胞存活中的重要作用。结果表明，ZIC5在PDAC和CCA组织中强烈表达，而在大多数正常成人组织中几乎未观察到ZIC5表达。此外，ZIC5表达与PDAC患者的不良预后相关。通过小干扰RNA敲低ZIC5可降低信号转导和转录激活因子3（STAT3）的磷酸化，STAT3是一种与PDAC和CCA侵袭性相关的蛋白质。然而，无论STAT3是否被激活，敲低ZIC5都会诱导细胞死亡，STAT3的激活由白细胞介素（IL）-6促进，IL-6是一种与炎症相关的因子。此外，在PDAC和CCA细胞中敲低ZIC5与抗癌药物吉西他滨联合或协同诱导细胞凋亡。因此，ZIC5构成了治疗PDAC和CCA的潜在治疗靶点。
