Xiaofeng Xu1, Xiangyi Kong1, Tao Liu2, Ling Zhou3, Jun Wu1, Jian Fu4, Yijin Wang5, Mengjing Zhu3, Shuang Yao3, Yue Ding2, Ling Ding1, Rong Li1, Xianghong Zhu1, Xiaoqiu Tang1, Yan Zhang1, Qian Yang6, Jingxian Ling7, Huaijun Zhou8. 1. Department of Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, People's Republic of China. 2. Medical College, Nanjing University, Nanjing 210008, People's Republic of China. 3. Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, People's Republic of China. 4. Department of Gynecology, Suqian People's Hospital of Nanjing Drum Tower Hospital Group, Suqian, 223800, People's Republic of China. 5. Medical College, Southeast University, Nanjing 210008, People's Republic of China. 6. Department of Gynecology and Obstetrics, The Pukou Hospital of Nanjing, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing 210031, People's Republic of China. 7. Department of Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, People's Republic of China. Electronic address: nj-ljx@163.com. 8. Department of Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, People's Republic of China. Electronic address: zhouhj2007@126.com.
Abstract
OBJECTIVE: Though metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with advanced clinicopathological characteristics and survival in related diseases, the association between MTA1 and endometrial cancer (EC) is little known and needs to be studied. METHODS: Western blot and immunohistochemistry were used to analyze protein expression level of cells and tissues, while real-time PCR was used for RNA detection. Bioinformatics tool analysis revealed the relationship between MTA1 and clinicopathological characteristics and survival. CCK-8 assay, colony-formation assay, cell scratch assay, and Transwell assay were performed to determine cell proliferation, migration and invasion abilities, respectively. RESULTS: The expression level of MTA1 was significantly higher in human EC tissues than in normal endometrium. MTA1 expression was correlated positively with lymph nodes metastasis and poor survival rate in EC. Experimentally overexpressed MTA1 could promote cell proliferation, migration and invasion abilities of EC cell lines Ishikawa, HEC-1B, and RL-952, while reduction of MTA1 inhibited these cell biological behaviors. Moreover, MTA1 could also reverse the negative effect of miR-30c, a direct modulator of MTA1, on EC cells. Our research also revealed that overexpression of MTA1 contributed to EC tumor growth, while knockdown of MTA1 resulted in tumor growth inhibition. Additionally, the phosphorylation levels of mTOR (S2448) and 4E-BP1 (T37/46) changed significantly along with AKT (T308) under regulation of MTA1, both in vivo and vitro. CONCLUSION: Our results showed that MTA1, as a downstream target of miR-30c, might promote EC progression via AKT/mTOR/4E-BP1 pathway, which indicated the potential therapy target of MTA1 in EC.
OBJECTIVE: Though metastasis-associated protein 1 (MTA1) is widely overexpressed in humancancers and is associated with advanced clinicopathological characteristics and survival in related diseases, the association between MTA1 and endometrial cancer (EC) is little known and needs to be studied. METHODS: Western blot and immunohistochemistry were used to analyze protein expression level of cells and tissues, while real-time PCR was used for RNA detection. Bioinformatics tool analysis revealed the relationship between MTA1 and clinicopathological characteristics and survival. CCK-8 assay, colony-formation assay, cell scratch assay, and Transwell assay were performed to determine cell proliferation, migration and invasion abilities, respectively. RESULTS: The expression level of MTA1 was significantly higher in human EC tissues than in normal endometrium. MTA1 expression was correlated positively with lymph nodes metastasis and poor survival rate in EC. Experimentally overexpressed MTA1 could promote cell proliferation, migration and invasion abilities of EC cell lines Ishikawa, HEC-1B, and RL-952, while reduction of MTA1 inhibited these cell biological behaviors. Moreover, MTA1 could also reverse the negative effect of miR-30c, a direct modulator of MTA1, on EC cells. Our research also revealed that overexpression of MTA1 contributed to EC tumor growth, while knockdown of MTA1 resulted in tumor growth inhibition. Additionally, the phosphorylation levels of mTOR (S2448) and 4E-BP1 (T37/46) changed significantly along with AKT (T308) under regulation of MTA1, both in vivo and vitro. CONCLUSION: Our results showed that MTA1, as a downstream target of miR-30c, might promote EC progression via AKT/mTOR/4E-BP1 pathway, which indicated the potential therapy target of MTA1 in EC.