中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Malat1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing mir-203 and promoting thymidylate synthase expression

文献类型:期刊论文

作者Chen, Wei1,2,3; Xu, Xin-Ke1; Li, Jun-liang1,2; Kong, Kuan-kei1,2; Li, Hui4; Chen, Cheng1; He, Jing1; Wang, Fangyu1; Li, Ping1; Ge, Xiao-song5
刊名Oncotarget
出版日期2017
卷号8期号:14页码:22783-22799
ISSN号1949-2553
关键词Malat1 Temozolomide Chemoresistance Mir-203 Thymidylate synthase
DOI10.18632/oncotarget.15199
通讯作者Ge, xiao-song(stanly8345@163.com) ; Li, fang-cheng(sjwklfc@126.com)
英文摘要Glioblastoma multiforme (gbm) is the most malignant brain tumor with limited therapeutic options. temozolomide (tmz) is a novel cytotoxic agent used as first-line chemotherapy for gbm, however, some individual cells can't be isolated for surgical resection and show treatment-resistance, thus inducing poor prognosis. by using the hiseq sequencing and bioinformatics methods, we identified lncrnas showing different expression levels in tmz-resistant and non-resistant patients. rt-qpcr was then performed in tissues and serum samples, and lncrna malat1 was finally identified to show considerable discriminating potential to identify responding patients from non-responding patients. moreover, high serum malat1 expression was associated with poor chemoresponse and survival in gbm patients receiving tmz treatment. subsequently, the tmz resistant cell lines were established, and the cck8 assay showed that lncrna malat1 knockdown significantly reversed tmz resistance in gbm cells. the gain and loss-function experiments revealed that mir-203 was downregulated by malat1 and this interaction has reciprocal effects. besides, thymidylate synthase (ts) mrna was identified as a direct target of mir-203. lncrna malat1 inhibition re-sensitized tmz resistant cells through up-regulating mir-203 and downregulating ts expression. on the other hand, malat1 overexpression promoted resistance by suppressing mir-203 and promoting ts expression. in conclusion, our integrated approach demonstrates that enhanced expression of lncrna malat1 confers a potent poor therapeutic efficacy and inhibition of malat1 levels could be a future direction to develop a novel therapeutic strategy to overcome tmz resistance in gbm patients.
WOS关键词NONCODING RNA MALAT1 ; COLORECTAL-CANCER CELLS ; DOWN-REGULATION ; MESENCHYMAL TRANSITION ; OXALIPLATIN RESISTANCE ; BRAIN-TUMORS ; STEM-CELLS ; GLIOMA ; PROLIFERATION ; TRANSCRIPTOME
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
语种英语
出版者IMPACT JOURNALS LLC
WOS记录号WOS:000398211100042
URI标识http://www.irgrid.ac.cn/handle/1471x/2373448
专题武汉病毒研究所
通讯作者Ge, Xiao-song; Li, Fang-cheng
作者单位1.Guangzhou Med Univ, Dept Neurosurg, Guangzhou Women & Childrens Med Ctr, Guangzhou 510623, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurosurg, Guangzhou 510120, Guangdong, Peoples R China
3.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
4.Sun Yat Sen Univ, Peoples Hosp Foshan 1, Dept Resp, Foshan 528000, Guangdong, Peoples R China
5.Jiangnan Univ, Dept Oncol, Affiliated Hosp, Wuxi 214062, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714
Chen, Wei,Xu, Xin-Ke,Li, Jun-liang,et al. Malat1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing mir-203 and promoting thymidylate synthase expression[J]. Oncotarget,2017,8(14):22783-22799.
APA Chen, Wei.,Xu, Xin-Ke.,Li, Jun-liang.,Kong, Kuan-kei.,Li, Hui.,...&Li, Fang-cheng.(2017).Malat1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing mir-203 and promoting thymidylate synthase expression.Oncotarget,8(14),22783-22799.
MLA Chen, Wei,et al."Malat1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing mir-203 and promoting thymidylate synthase expression".Oncotarget 8.14(2017):22783-22799.

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来源:武汉病毒研究所

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