title: The effect of JAK2 knockout on inhibition of liver tumor growth by inducing apoptosis, autophagy and anti-proliferation via STATs and PI3K/AKT signaling pathways.
abstract: Liver cancer is a leading cause of cancer death, making it as the second most common cause for death from cancer globally. Though many studies before have explored a lot for liver cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. Therefore, we were aimed to investigate the underlying mechanisms by which JAK2 performed its role in ameliorating liver cancer. JAK2 knockout liver cancer cell lines were involved for our experiments in vitro and in vivo. Western blotting, quantitative RT-PCR (qRT-PCR), ELISA, Immunohistochemistry, and flow-cytometric analysis were used to determine the key signaling pathway regulated by JAK2 for liver cancer progression. Data here indicated that JAK2, indeed, expressed highly in cancer cell lines compared to the normal liver cells. And apoptosis and autophagy were found in JAK2 knockout liver cancer cells through activating Caspase-3, Cyclin-D1 and mTOR regulated by STAT3/5 and PI3K/AKT signaling pathway. And also, the liver cancer cells proliferation was inhibited. In addition, tumor size and weight were reduced by knockout of JAK2 in vivo experiments. These findings demonstrated that JAK2 and its down-streaming signaling pathways play a direct role in the progression of liver cancer possibly. To our knowledge, it was the first time to evaluate the role of JAK2 knockout in improving liver cancer from apoptosis, autophagy and proliferation, which could be a potential target for future therapeutic approach clinically.
authors: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, China. Electronic address: xuying223300@163.com.
authors: Ying
authors: Y
authors: Xu
authors: Department of Gastroenterology, The Second Pepole's Hospital of Huai'an, Xuzhou Medical University, Huaihai South Road, Huai'an, Jiangsu 223300, China.
authors: Sheng-Xiang
authors: SX
authors: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; Autophagy; JAK2 knockout; Liver cancer; Proliferation