HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration/invasion via targeting miR-221/222 in cervical cancer.
HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration/invasion via targeting miR-221/222 in cervical cancer.
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HMGA1 通过调节细胞周期加剧肿瘤生长，并通过靶向宫颈癌中的 miR-221/222 加速迁移/侵袭
DOI：
10.1038/s41419-018-0683-x
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发表时间：
2018-05-22
影响因子：
9
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Fu F;Wang T;Wu Z;Feng Y;Wang W;Zhou S;Ma X;Wang S
高迁移率组 AT-hook1（HMGA1，以前的 HMG-I/Y）是一种结构转录因子，参与许多肿瘤生物学过程。然而，它对宫颈癌的影响仍然不明确。本研究发现HMGA1在宫颈癌组织中普遍过表达,且与淋巴结转移及临床晚期呈正相关。通过外源增加或减少HMGA1的表达，我们发现HMGA1在体外影响宫颈癌细胞的增殖、集落形成、迁移和侵袭。救援实验表明，miR-221/222 可以部分逆转 HMGA1 介导的迁移和侵袭过程。从机制上讲，我们发现HMGA1通过调节cyclin D1和cyclin E1的表达来加速G1/S相变，这与体内实验的结果一致。此外，我们发现HMGA1在转录水平上调节miR-221/222簇的表达，并且miR-221/222靶向金属蛋白酶组织抑制剂3（TIMP3）的3'UTR。我们提出了一个新的视角，即HMGA1通过miR-221/222-TIMP3-MMP2/MMP9轴参与宫颈癌的迁移和侵袭过程。总之，我们的研究确定了 HMGA1 在宫颈癌进展中发挥的关键作用及其发挥作用的潜在机制，表明靶向 HMGA1 相关通路可能有利于宫颈癌的治疗。
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.
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影响因子：
82.9
作者：
Foti, D;Chiefari, E;Brunetti, A
通讯作者：
Brunetti, A
影响因子：
7.5
作者：
Chen, Dan;Yan, Wangxiang;Chen, Yu
通讯作者：
Chen, Yu
影响因子：
4.6
作者：
Fujikane R;Komori K;Sekiguchi M;Hidaka M
通讯作者：
Hidaka M
影响因子：
14.9
作者：
Altuvia Y;Landgraf P;Lithwick G;Elefant N;Pfeffer S;Aravin A;Brownstein MJ;Tuschl T;Margalit H
通讯作者：
Margalit H
DOI：
10.1073/pnas.91.24.11318
发表时间：
1994-11-22
影响因子：
11.1
作者：
DU, W;MANIATIS, T
通讯作者：
MANIATIS, T