MiR-744-5p inducing cell death by directly targeting HNRNPC and NFIX in ovarian cancer cells.
MiR-744-5p inducing cell death by directly targeting HNRNPC and NFIX in ovarian cancer cells.
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DOI：
10.1038/s41598-018-27438-6
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发表时间：
2018-06-13
影响因子：
4.6
通讯作者：
Otte K
中科院分区：
文献类型：
--
作者：
Kleemann M;Schneider H;Unger K;Sander P;Schneider EM;Fischer-Posovszky P;Handrick R;Otte K
MicroRNAs(MiRNAs)在基因表达调控中发挥着重要作用。与靶信使RNA(MRNAs)的结合导致mRNA的切割或翻译机制的抑制，从而导致蛋白质水平下降。包括细胞凋亡在内的多种信号通路都受到miRNAs的调控。在这里，我们研究了miR-744-5p在卵巢癌细胞系中的凋亡信号转导中的作用。在不依赖宿主基因MAP2K4的癌细胞系中，MIR-744-5p的表达降低。MiR-744-5p的过表达激活了SKOV3、OVCAR3、顺铂耐药(A2780-cis)和非耐药A2780细胞的内源性凋亡途径，导致细胞死亡。值得注意的是，miR-744-5p的过度表达与卡铂治疗一起导致了至少相加的促凋亡作用。对miR-744-5p介导的细胞凋亡信号通路的研究表明，其表达上调直接下调核因子I X(NFIX)和异质性核糖核蛋白C(HNRNPC)的mRNA和蛋白表达。HNRNPC导致miR-21表达减少和AKT磷酸化，而NFIX降低bcl2水平，导致检测到的促凋亡作用。最后，Kaplan-Meier图显示，miR-744高表达的卵巢浆液性囊腺癌患者的中位无病生存期延长。
MicroRNAs (miRNAs) play an important role in the regulation of gene expression. The binding to target messenger RNAs (mRNAs) results in mRNA cleavage or inhibition of the translational machinery leading to decreased protein levels. Various signalling pathways, including apoptosis are modulated by miRNAs. Here, we investigated the role of miR-744-5p in apoptosis signalling in ovarian cancer cell lines. MiR-744-5p expression was reduced in the cancer cell lines independent of the host gene MAP2K4. Overexpression of miR-744-5p activated the intrinsic apoptotic pathway in SKOV3, OVCAR3 and Cisplatin resistant (A2780-cis) and non-resistant A2780 cells leading to cell death. Notably, miR-744-5p overexpression together with Carboplatin treatment led to at least additive pro-apoptotic effects. Investigation of the apoptotic signalling pathways mediated by miR-744-5p revealed that its elevated expression directly downregulated mRNA and protein expression of nuclear factor I X (NFIX) and heterogeneous nuclear ribonucleoprotein C (HNRNPC). HNRNPC caused diminished miR-21 expression and AKT phosphorylation, while NFIX decreased Bcl2 levels, leading to the detected pro-apoptotic effects. Finally, Kaplan-Meier-Plots showed a prolonged median disease-free survival in ovarian serous cystadenocarcinoma patients with high miR-744 expression.
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影响因子：
20.3
作者：
Holmfeldt, Per;Pardieck, Jennifer;McKinney-Freeman, Shannon
通讯作者：
McKinney-Freeman, Shannon
影响因子：
4.1
作者：
Fischer, Simon;Wagner, Andreas;Otte, Kerstin
通讯作者：
Otte, Kerstin
影响因子：
7.4
作者：
Kobayashi M;Salomon C;Tapia J;Illanes SE;Mitchell MD;Rice GE
通讯作者：
Rice GE
影响因子：
4.6
作者：
Cole AJ;Dwight T;Gill AJ;Dickson KA;Zhu Y;Clarkson A;Gard GB;Maidens J;Valmadre S;Clifton-Bligh R;Marsh DJ
通讯作者：
Marsh DJ
影响因子：
7.5
作者：
Chen, Xiao-Fang;Liu, Yun
通讯作者：
Liu, Yun