Department of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju-do, 63243, Republic of Korea.
Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea.
Cell Oncol (Dordr). 2020 Oct;43(5):821-834. doi: 10.1007/s13402-020-00527-3. Epub 2020 Jun 1.
Pancreatic cancer is one of the most aggressive cancers. Preclinical and clinical data indicate that Notch 1 ligand jagged1 (JAG1) plays a pro-oncogenic role in several malignant cancers. As yet, however, the role of JAG1 in pancreatic cancer is poorly understood. The objective of the present study was to investigate JAG1 as a therapeutic target in human pancreatic cancer.
Expression levels of Notch signaling molecules were assessed using GEO datasets and Western blot analysis, respectively. Anti-tumor effects following JAG1 silencing were evaluated using in vitro and in vivo assays. Prognostic implications were assessed using GEO datasets.
Using GEO datasets and Western blot analysis we detected significantly higher JAG1 mRNA and protein expression levels in pancreatic cancer compared to normal pancreatic tissues. JAG1 silencing significantly restrained the growth, migration and invasion of pancreatic cancer cells through the induction of apoptosis and blockade of various kinases independent of the Notch1 pathway. Combined JAG1 silencing and gemcitabine treatment showed synergistic anti-viability effects in human pancreatic cancer cells. JAG1 silencing also resulted in significant anti-cancer effects in vivo and high JAG1 expression was found to be associated with an adverse prognosis in pancreatic cancer patients.
From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer.
胰腺癌是最具侵袭性的癌症之一。临床前和临床数据表明，Notch 1 配体 Jagged1（JAG1）在几种恶性肿瘤中发挥致癌作用。然而，目前对于 JAG1 在胰腺癌中的作用知之甚少。本研究旨在探讨 JAG1 作为人类胰腺癌的治疗靶点。
使用 GEO 数据集和 Western blot 分析分别评估 Notch 信号分子的表达水平。使用体外和体内实验评估 JAG1 沉默后的抗肿瘤效果。使用 GEO 数据集评估预后意义。
通过 GEO 数据集和 Western blot 分析，我们检测到与正常胰腺组织相比，胰腺癌中 JAG1 mRNA 和蛋白表达水平显著升高。JAG1 沉默通过诱导细胞凋亡和阻断 Notch1 途径以外的多种激酶，显著抑制胰腺癌细胞的生长、迁移和侵袭。JAG1 沉默联合吉西他滨治疗可在人胰腺癌细胞中产生协同的抗活力效应。JAG1 沉默还在体内产生了显著的抗癌作用，并且高 JAG1 表达与胰腺癌患者的不良预后相关。
根据我们的数据，我们得出结论，JAG1 可能是胰腺癌有前途的治疗靶点。
