TRIM28(Tripartite motif-containing protein 28), a member of TRIM family, is aberrantly expressed and reportedly has different functions in many types of human cancer. However, the biological roles of TRIM28 and relate...TRIM28(Tripartite motif-containing protein 28), a member of TRIM family, is aberrantly expressed and reportedly has different functions in many types of human cancer. However, the biological roles of TRIM28 and related mechanism in colorectal cancer(CRC) remain unclear. Here, we showed that TRIM28 was downregulated in colorectal cancer compared with normal mucosa, especially at advanced stages, and acted as an independent prognostic factor of favorable outcome. Functional studies demonstrated that TRIM28 restrained CRC migration and invasion in vitro and in vivo. Mechanistically, we reported that CARM1(co-activator-associated arginine methyltransferase1) was a critical player downstream of TRIM28. TRIM28 interacted with CARM1, and protected CARM1 from proteasome-mediated degradation through physical protein-protein interaction to suppress CRC metastasis. Further, TRIM28 suppressed the migration and invasion of CRC cells through inhibiting WNT/b-catenin signaling in a CARM1-dependent manner, but independent of CARM10 s methyltransferase activity. The protein expression of CARM1 was positively correlated with TRIM28 in CRC tissues. Patients with high levels of TRIM28 and CARM1 had improved prognosis, whereas patients with low TRIM28 and CARM1 expression had the poor outcomes. Thus, our study reveals an inhibitory role of TRIM28 in CRC metastasis, which was achieved through a TRIM28-CARM1-WNT/b-catenin axis. This work provides potential prognostic and therapeutic targets for CRC treatment.展开更多
目的:探讨TRIM28在肺癌中的表达情况,与肺癌临床病理特征的关系,评估其在肺癌中的预后价值。方法:下载美国国立生物信息技术中心(National Center for Biotechnology Information,NCBI)的肺癌样本数据集GSE30219,对表达谱资料及临床信...目的:探讨TRIM28在肺癌中的表达情况,与肺癌临床病理特征的关系,评估其在肺癌中的预后价值。方法:下载美国国立生物信息技术中心(National Center for Biotechnology Information,NCBI)的肺癌样本数据集GSE30219,对表达谱资料及临床信息进行分析。结果:TRIM28在肺癌组织中高表达,在高TNM分期肿瘤中高表达(P均<0.01)。在不同性别、AJCC T分期、有无区域淋巴结转移、远处转移、复发的肺癌患者中,TRIM28的表达均有显著性差异(P均<0.05)。TRIM28高表达与肺癌患者(HR=1.49,95%CI=1.31~1.69,P<0.01)、肺腺癌患者(HR=2.12,95%CI=1.66~2.7,P<0.01)、不吸烟患者(HR=3.56,95%CI=1.89~6.72,P<0.01)和吸烟患者(HR=1.26,95%CI=1.02~1.55,P<0.05)的预后不良相关,还可作为临床Ⅰ期(HR=2.4,95%CI=1.81~3.2,P<0.01)、Ⅱ期(HR=1.6,95%CI=1.11~2.32,P<0.05)和化疗(HR=1.66,95%CI=1.11~2.49,P<0.05)患者预后的危险因素。结论:TRIM28高表达与肺癌多个临床病理指标和患者预后不良相关,可以作为潜在的判断肺癌患者预后的标志物和肿瘤治疗的靶点。展开更多
基金supported by the Major State Basic Research Development Program of China (2015CB554007)the National Natural Science Foundation of China (81572866, 81773263 81773104, 31701202)+5 种基金the International Science and Technology Corporation Program of Chinese Ministry of Science and Technology (2014DFA32920)the Science and Technology Program of Chinese Ministry of Education (113044A)the Frontier Exploration Program of Huazhong University of Science and Technology (2015TS153)the Natural Science Foundation Program of Hubei Province (2015CFA049)the Research Fund of Public Welfare in Health Industry (201402015)the Research Fund of Public Welfare in Health Industry (201402015) from the Health and Family Plan Committee of China
文摘TRIM28(Tripartite motif-containing protein 28), a member of TRIM family, is aberrantly expressed and reportedly has different functions in many types of human cancer. However, the biological roles of TRIM28 and related mechanism in colorectal cancer(CRC) remain unclear. Here, we showed that TRIM28 was downregulated in colorectal cancer compared with normal mucosa, especially at advanced stages, and acted as an independent prognostic factor of favorable outcome. Functional studies demonstrated that TRIM28 restrained CRC migration and invasion in vitro and in vivo. Mechanistically, we reported that CARM1(co-activator-associated arginine methyltransferase1) was a critical player downstream of TRIM28. TRIM28 interacted with CARM1, and protected CARM1 from proteasome-mediated degradation through physical protein-protein interaction to suppress CRC metastasis. Further, TRIM28 suppressed the migration and invasion of CRC cells through inhibiting WNT/b-catenin signaling in a CARM1-dependent manner, but independent of CARM10 s methyltransferase activity. The protein expression of CARM1 was positively correlated with TRIM28 in CRC tissues. Patients with high levels of TRIM28 and CARM1 had improved prognosis, whereas patients with low TRIM28 and CARM1 expression had the poor outcomes. Thus, our study reveals an inhibitory role of TRIM28 in CRC metastasis, which was achieved through a TRIM28-CARM1-WNT/b-catenin axis. This work provides potential prognostic and therapeutic targets for CRC treatment.
文摘目的:探讨TRIM28在肺癌中的表达情况,与肺癌临床病理特征的关系,评估其在肺癌中的预后价值。方法:下载美国国立生物信息技术中心(National Center for Biotechnology Information,NCBI)的肺癌样本数据集GSE30219,对表达谱资料及临床信息进行分析。结果:TRIM28在肺癌组织中高表达,在高TNM分期肿瘤中高表达(P均<0.01)。在不同性别、AJCC T分期、有无区域淋巴结转移、远处转移、复发的肺癌患者中,TRIM28的表达均有显著性差异(P均<0.05)。TRIM28高表达与肺癌患者(HR=1.49,95%CI=1.31~1.69,P<0.01)、肺腺癌患者(HR=2.12,95%CI=1.66~2.7,P<0.01)、不吸烟患者(HR=3.56,95%CI=1.89~6.72,P<0.01)和吸烟患者(HR=1.26,95%CI=1.02~1.55,P<0.05)的预后不良相关,还可作为临床Ⅰ期(HR=2.4,95%CI=1.81~3.2,P<0.01)、Ⅱ期(HR=1.6,95%CI=1.11~2.32,P<0.05)和化疗(HR=1.66,95%CI=1.11~2.49,P<0.05)患者预后的危险因素。结论:TRIM28高表达与肺癌多个临床病理指标和患者预后不良相关,可以作为潜在的判断肺癌患者预后的标志物和肿瘤治疗的靶点。
