Zic family member 5 promotes survival in human pancreatic cancer and cholangiocarcinoma cells.
Zic family member 5 promotes survival in human pancreatic cancer and cholangiocarcinoma cells.
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DOI：
10.1016/j.bbrep.2022.101289
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发表时间：
2022-09
影响因子：
2.7
通讯作者：
Fukami, Kiyoko
中科院分区：
文献类型：
--
作者：
Satow, Reiko;Aiga, Yuna;Watanabe, Takeru;Ishizuka, Nako;Yoneda, Atsuko;Fukami, Kiyoko
胰腺导管腺癌（PDAC）和胆管癌（CCA）是由于传统化疗效果有限且有效的分子治疗药物很少而导致预后不良的恶性肿瘤。在这里，我们确定了 Zic 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ZIC5在大多数正常成人组织中几乎观察不到表达。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 会降低信号转导子和转录激活子 3 (STAT3) 的磷酸化，STAT3 是一种与 PDAC 和 CCA 攻击性相关的蛋白质。然而，无论 STAT3 激活如何，ZIC5 敲低都会诱导细胞死亡，而 STAT3 激活是由白细胞介素 (IL) -6（一种与炎症相关的因子）促进的。此外，PDAC和CCA细胞中ZIC5的敲低可与抗癌药物吉西他滨相加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。 ZIC5 在 PDAC 和 CCA 中表达，而在正常成人组织中几乎观察不到。 ZIC5表达与PDAC患者不良预后相关。 ZIC5 敲低可诱导多种 PDAC 和 CCA 细胞系凋亡。 ZIC5 的敲低与吉西他滨相加或协同诱导细胞凋亡。
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 (ZIC5) in the survival of PDAC and CCA cells. The results showed that ZIC5 is strongly expressed in PDAC and CCA tissues, while ZIC5 expression is barely observed in most normal human adult tissues. Furthermore, ZIC5 expression is related to poor prognosis of patients with PDAC. ZIC5 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, ZIC5 knockdown induced cell death regardless of STAT3 activation, which is promoted by interleukin (IL) −6, a factor associated with inflammation. Furthermore, knockdown of ZIC5 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. ZIC5 is expressed in PDAC and CCA, while barely observed in normal adult tissues. ZIC5 expression is related to poor prognosis of patients with PDAC. ZIC5 knockdown induces apoptosis in several PDAC and CCA cell lines. Knockdown of ZIC5 additively or synergistically induces apoptosis with gemcitabine.
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影响因子：
11.2
作者：
Nagathihalli NS;Castellanos JA;Lamichhane P;Messaggio F;Shi C;Dai X;Rai P;Chen X;VanSaun MN;Merchant NB
通讯作者：
Merchant NB
影响因子：
29.4
作者：
Isomoto, Hajime;Mott, Justin L.;Gores, Gregory J.
通讯作者：
Gores, Gregory J.
影响因子：
50.3
作者：
Fukuda A;Wang SC;Morris JP 4th;Folias AE;Liou A;Kim GE;Akira S;Boucher KM;Firpo MA;Mulvihill SJ;Hebrok M
通讯作者：
Hebrok M
影响因子：
5.8
作者：
Wong, Nathan W.;Chen, Yuhao;Wang, Xiaowei
通讯作者：
Wang, Xiaowei
影响因子：
4
作者：
Hao, Liguo;Rong, Wei;Meng, Xin
通讯作者：
Meng, Xin