机构：[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]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[3]University of Chinese Academy of Sciences, Beijing 100049, China[4]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China[5]Oncology and Hematology Department, Mianyang Hospital of T.C.M., Mianyang 621000, Sichuan, China[6]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[7]Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China重庆医科大学附属第一医院[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
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.
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.
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.
TRIM44 was associated with oncogenic potential of glioma. Targeting TRIM44 might be beneficial for glioma therapy.
基金：
National Natural Science
Foundation of China (NSFC, Grant No. 81472862), the Top
Talents Program of Yunnan Province China (Grant No. 2012HA014)
to Xudong Zhao, Applied Basic Research Projects of Yunnan (Grant
No. 2013FA020), the National Key Research and Development Program
of China (Grant Nos. 2016YFC0901701, 2017YFC0908402,
2018YFC0910702, 2018YFC0910402), the China Postdoctoral Science
Foundation (Project No: 2019M653500, awarded to Xia Zhou).
第一作者机构：[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[6]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
共同第一作者：
通讯作者：
通讯机构：[2]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[3]University of Chinese Academy of Sciences, Beijing 100049, China
推荐引用方式(GB/T 7714)：
Xia Zhou,Yadong Yang,Pengcheng Ma,et al.TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway.[J].JOURNAL OF NEURO-ONCOLOGY.2019,145(2):211-222.doi:10.1007/s11060-019-03301-0.
APA：
Xia Zhou,Yadong Yang,Pengcheng Ma,Na Wang,Dong Yang...&Xiangdong Fang.(2019).TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway..JOURNAL OF NEURO-ONCOLOGY,145,(2)
MLA：
Xia Zhou,et al."TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway.".JOURNAL OF NEURO-ONCOLOGY 145..2(2019):211-222
