Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA-101 in glioblastoma.
Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA-101 in glioblastoma.
复制标题
DOI：
10.1002/cam4.1384
复制
发表时间：
2018-04
期刊：
影响因子：
4
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
Cai T;Liu Y;Xiao J
胶质母细胞瘤（GBM）是中枢神经系统最常见和最致命的肿瘤，具有高度浸润性和耐化疗性。替莫唑胺（TMZ）被广泛用作治疗GBM的一线治疗。然而，GBM中相当大比例的固有或获得性耐药是TMZ化疗的许多治疗失败的原因。因此，深入了解TMZ耐药的分子特征和寻找新的治疗靶点是当务之急。在这里，我们发现MALAT 1在TMZ耐药GBM细胞中显著上调。另一方面，MALAT 1敲低通过抑制细胞增殖和促进细胞凋亡降低体外和体内GBM细胞的TMZ抗性。我们还发现，与MALAT 1相比，miR-101过表达降低了GBM细胞的TMZ耐药性，并发挥了拮抗作用。重要的是，我们证明了MALAT 1通过直接结合GBM细胞中的miR-101信号通路来抑制miR-101信号通路，从而促进化疗耐药性。总之，我们的研究表明，MALAT 1的敲除通过促进GBM中的miR-101调控网络逆转了对TMZ的化疗耐药性，从而为GBM TMZ化疗提供了一种新的预后标志物和潜在靶点。
Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system with highly infiltrative and resistant to chemotherapy. Temozolomide (TMZ) is widely used as the first‐line treatment for the therapy of GBM. However, a considerable percentage inherent or acquired resistance in GBM accounts for many treatment failures of the TMZ chemotherapy. Therefore, a deeper understanding of the molecular characteristics underlying TMZ resistance and the identification of novel therapeutic target is urgent. Here, we show that MALAT1 was significantly upregulated in TMZ‐resistant GBM cells. On the other hand, MALAT1 knockdown reduces TMZ resistance of GBM cells both in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. We also show that miR‐101 overexpression reduced TMZ resistance of GBM cells and played an antagonistic role compared with MALAT1. Importantly, we demonstrate that MALAT1 promoted the chemoresistance through suppressing miR‐101 signaling pathway via directly binding it in GBM cells. In conclusion, our study indicates that knockdown of MALAT1 reverses chemoresistance to TMZ via promoting miR‐101 regulatory network in GBM and thus offers a novel prognostic marker and potential target for GBM TMZ‐based chemotherapy.
登录
查看更多内容
影响因子：
11.5
作者：
Fan, Yu;Shen, Bing;Liu, Yong
通讯作者：
Liu, Yong
影响因子：
--
作者：
Konno Y;Dong P;Xiong Y;Suzuki F;Lu J;Cai M;Watari H;Mitamura T;Hosaka M;Hanley SJ;Kudo M;Sakuragi N
通讯作者：
Sakuragi N
影响因子：
4.5
作者：
Tripathi V;Shen Z;Chakraborty A;Giri S;Freier SM;Wu X;Zhang Y;Gorospe M;Prasanth SG;Lal A;Prasanth KV
通讯作者：
Prasanth KV
TAZ 通过上调人胶质瘤细胞中的 MCL-1 促进替莫唑胺耐药
DOI：
10.1016/j.bbrc.2015.05.115
发表时间：
2015-08-07
影响因子：
3.1
作者：
Tian, Tian;Li, Aimin;Li, Zhaoming
通讯作者：
Li, Zhaoming
DOI：
10.1007/978-3-319-42059-2_11
发表时间：
2016-01-01
期刊：
NON-CODING RNAS IN COLORECTAL CANCER
影响因子：
--
作者：
Fanale, Daniele;Castiglia, Marta;Russo, Antonio
通讯作者：
Russo, Antonio