Journal Article

HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration/invasion via targeting miR-221/222 in cervical cancer

Wu, Zhangying, Ma, Xiangyi, Wang, Wenwen, Feng, Yourong, Wang, Shixuan, Zhou, Su, Fu, Fangfang, Wang, Tian

2018

Overview

High-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), an architectural transcription factor, participates in a number of tumor biological processes. However, its effect on cervical cancer remains largely indistinct. In this study, we found that HMGA1 was generally overexpressed in cervical cancer tissues and was positively correlated with lymph node metastasis and advanced clinical stage. Via exogenously increasing or decreasing the expression of HMGA1, we showed that HMGA1 affected the proliferation, colony formation, migration and invasion of cervical cancer cells in vitro. Rescue experiments suggested that miR-221/222 could partly reverse HMGA1-mediated migration and invasion processes. Mechanistically, we discovered that HMGA1 accelerated the G1/S phase transition by regulating the expression of cyclin D1 and cyclin E1, which was consistent with the results of the in vivo experiment. Furthermore, we found that HMGA1 regulated the expression of the miR-221/222 cluster at the transcriptional level and that miR-221/222 targeted the 3'UTR of tissue inhibitor of metalloproteinases 3(TIMP3). We propose a fresh perspective that HMGA1 participates in the migration and invasion process via the miR-221/222-TIMP3-MMP2/MMP9 axis in cervical cancer. In summary, our study identified a critical role played by HMGA1 in the progression of cervical cancer and the potential mechanisms by which exerts its effects, suggesting that targeting HMGA1-related pathways could be conducive to the therapies for cervical cancer.

• Publisher: Springer Nature B.V,Nature Publishing Group UK
• Subject: 3' Untranslated regions / Base Sequence / Cell cycle / Cell Cycle - genetics / Cell Line, Tumor / Cell migration / Cell Movement - genetics / Cell proliferation / Cell Proliferation - genetics / Cervical cancer / Clone Cells / Cyclin D1 / Cyclin D1 - metabolism / Cyclin E - metabolism / Epithelium - metabolism / Epithelium - pathology / Female / G1 Phase - genetics / Gelatinase A / Gelatinase B / Gene Expression Regulation, Neoplastic / HMGA1a Protein - metabolism / Human papillomavirus / Humans / Lymph nodes / Matrix Metalloproteinases - metabolism / Metastases / MicroRNAs - genetics / MicroRNAs - metabolism / Middle Aged / Models, Biological / Neoplasm Invasiveness / Phase transitions / S phase / S Phase - genetics / Tissue inhibitor of metalloproteinase 3 / Tissue Inhibitor of Metalloproteinase-3 - metabolism / Tumor Stem Cell Assay / Uterine Cervical Neoplasms - genetics / Uterine Cervical Neoplasms - pathology