Xia Zhou1,2, Yadong Yang3,4, Pengcheng Ma5, Na Wang6,7, Dong Yang2, Qiu Tu1,2, Bin Sun2, Tingxiu Xiang7, Xudong Zhao2,8,9, Zongliu Hou10, Xiangdong Fang11,12. 1. Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Central Laboratory of Yan'an Hospital, Affiliated to Kunming Medical University, 245 East Ren Ming Road, Kunming, 650051, Yunnan, China. 2. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China. 3. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing, 100101, China. 4. University of Chinese Academy of Sciences, Beijing, 100049, China. 5. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China. 6. Oncology and Hematology Department, Mianyang Hospital of T.C.M., Mianyang, 621000, Sichuan, China. 7. Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. 8. Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China. 9. KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215000, Jiangsu, China. 10. Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Central Laboratory of Yan'an Hospital, Affiliated to Kunming Medical University, 245 East Ren Ming Road, Kunming, 650051, Yunnan, China. HZL579@163.com. 11. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing, 100101, China. fangxd@big.ac.cn. 12. University of Chinese Academy of Sciences, Beijing, 100049, China. fangxd@big.ac.cn.
Abstract
PURPOSE: Glioma is one of the lethal cancers which needs effective therapeutic target. TRIM44 has been found playing a carcinogenic role in human tumors such as breast cancer and ovarian cancer. However, the pathophysiological significance of TRIM44 in glioma is still unclear. METHODS: Quantitative-PCR and western blot were used to assess the expression of TRIM44 in glioma cells. For cell proliferation, Brdu incorporation and colony formation assays were performed. By Caspase 3 staining and FACS analysis, we revealed that TRIM44 knockdown induced glioma cell apoptosis. A BALB/c nude mouse xenograft model and following immunohistochemical (IHC) staining enables us to explore the effect of TRIM44 deletion on glioma growth in vivo. Western blot of p21, p27 and AKT indicated the possible role of TRIM44 in regulation AKT pathway in glioma. RESULTS: TRIM44 was significantly elevated in glioma cells, and high expression of TRIM44 is related to poor prognostic of glioma patients. TRIM44 knockdown by shRNAs inhibit glioma cell proliferation, migration, induced cell cycle disruption and further cellular apoptosis in vitro. As well, TRIM44 inactivation obviously inhibit tumor growth in xenograft model. Furthermore, the negative cell cycle regulators p21/p27 are significantly upregulated, while AKT which is known as the main regulator of p21/p27 is inactivated in TRIM44-dificient cells. These results suggested that TRIM44 inactivation disrupted cell cycle progression and inhibit cell proliferation through AKT/p21/p27 pathway in glioma. CONCLUSION: TRIM44 was associated with oncogenic potential of glioma. Targeting TRIM44 might be beneficial for glioma therapy.
PURPOSE:Glioma is one of the lethal cancers which needs effective therapeutic target. TRIM44 has been found playing a carcinogenic role in humantumors such as breast cancer and ovarian cancer. However, the pathophysiological significance of TRIM44 in glioma is still unclear. METHODS: Quantitative-PCR and western blot were used to assess the expression of TRIM44 in glioma cells. For cell proliferation, Brdu incorporation and colony formation assays were performed. By Caspase 3 staining and FACS analysis, we revealed that TRIM44 knockdown induced glioma cell apoptosis. A BALB/c nude mouse xenograft model and following immunohistochemical (IHC) staining enables us to explore the effect of TRIM44 deletion on glioma growth in vivo. Western blot of p21, p27 and AKT indicated the possible role of TRIM44 in regulation AKT pathway in glioma. RESULTS:TRIM44 was significantly elevated in glioma cells, and high expression of TRIM44 is related to poor prognostic of gliomapatients. TRIM44 knockdown by shRNAs inhibit glioma cell proliferation, migration, induced cell cycle disruption and further cellular apoptosis in vitro. As well, TRIM44 inactivation obviously inhibit tumor growth in xenograft model. Furthermore, the negative cell cycle regulators p21/p27 are significantly upregulated, while AKT which is known as the main regulator of p21/p27 is inactivated in TRIM44-dificient cells. These results suggested that TRIM44 inactivation disrupted cell cycle progression and inhibit cell proliferation through AKT/p21/p27 pathway in glioma. CONCLUSION:TRIM44 was associated with oncogenic potential of glioma. Targeting TRIM44 might be beneficial for glioma therapy.
Authors: Christopher J Peters; Jonathan R E Rees; Richard H Hardwick; James S Hardwick; Sarah L Vowler; Chin-Ann J Ong; Chunsheng Zhang; Vicki Save; Maria O'Donovan; Doris Rassl; Derek Alderson; Carlos Caldas; Rebecca C Fitzgerald Journal: Gastroenterology Date: 2010-06-02 Impact factor: 22.682
Authors: Sheila K Singh; Ian D Clarke; Mizuhiko Terasaki; Victoria E Bonn; Cynthia Hawkins; Jeremy Squire; Peter B Dirks Journal: Cancer Res Date: 2003-09-15 Impact factor: 12.701