Metastasis-associated protein 1, modulated by miR-30c, promotes endometrial cancer progression through AKT/mTOR/4E-BP1 pathway.

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.

• Authors: Xiaofeng Xu, Xiangyi Kong, Tao Liu, Ling Zhou, Jun Wu, Jian Fu, Yijin Wang, Mengjing Zhu, Shuang Yao, Yue Ding, Ling Ding, Rong Li, Xianghong Zhu, Xiaoqiu Tang, Yan Zhang, Qian Yang, Jingxian Ling, Huaijun Zhou
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 154 Issue 1 Pg. 207-217 (07 2019) ISSN: 1095-6859 [Electronic] United States
• PMID: 30979588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Adaptor Proteins, Signal Transducing
• Cell Cycle Proteins
• EIF4EBP1 protein, human
• MIRN30b microRNA, human
• MicroRNAs
• MTA1 protein, human
• Phosphoproteins
• Repressor Proteins
• Trans-Activators
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Histone Deacetylases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Cell Cycle Proteins
• Cell Movement
• Cell Proliferation
• Disease Progression
• Endometrial Neoplasms (genetics, metabolism, pathology)
• Female
• Heterografts
• Histone Deacetylases (biosynthesis, genetics, metabolism)
• Humans
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Phosphoproteins (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Repressor Proteins (biosynthesis, genetics, metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Trans-Activators
• Tumor Cells, Cultured