Jungwhoi Lee1, Jungsul Lee2, Jae Hoon Kim3,4. 1. Department of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju-do, 63243, Republic of Korea. sdjd1108@kaist.ac.kr. 2. Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea. 3. Department of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju-do, 63243, Republic of Korea. jhkim@jejunu.ac.kr. 4. Subtropical/tropical Organism Gene Bank, Jeju National University, Jeju-do, 63243, Republic of Korea. jhkim@jejunu.ac.kr.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer.
PURPOSE: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 humanpancreatic cancer. METHODS: 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. RESULTS: 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 humanpancreatic 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 cancerpatients. CONCLUSIONS: From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer.
Authors: Dina V Antonova; Marina V Zinovyeva; Liya G Kondratyeva; Alexander V Sass; Irina V Alekseenko; Victor V Pleshkan Journal: Int J Mol Sci Date: 2021-03-24 Impact factor: 5.923