RECQL4, Negatively Regulated by miR-10a-5p, Facilitates Cell Proliferation and Invasion via MAFB in Ovarian Cancer.
RECQL4, Negatively Regulated by miR-10a-5p, Facilitates Cell Proliferation and Invasion via MAFB in Ovarian Cancer.
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RECQL4，受 miR-10a-5p 负调控，通过 MAFB 促进卵巢癌细胞增殖和侵袭
DOI：
10.3389/fonc.2020.524128
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发表时间：
2020
影响因子：
4.7
通讯作者：
Kong B
中科院分区：
文献类型：
--
作者：
Guo L;Li Y;Zhao C;Peng J;Song K;Chen L;Zhang P;Ma H;Yuan C;Yan S;Fang Y;Kong B
与点突变相反，体细胞拷贝数改变的高频率被认为是卵巢癌的独特特征。参与DNA复制和修复的RecQ蛋白样4（RECQL 4）的扩增依赖性过表达介导了各种癌症的发展，但其病理生物学和临床作用知之甚少。在这里，使用生物信息学分析，发现RECQL 4扩增发生在TCGA队列中27%的卵巢癌样本中。基于卵巢癌的免疫组织化学染色，RECQL 4被发现上调并与不良预后相关。在功能上，RECQL 4过表达增加了卵巢癌细胞的增殖和侵袭。RECQL 4沉默具有相反的效果。此外，RECQL 4敲低增强了卵巢癌细胞对顺铂和PARP抑制剂（PARPi）的敏感性。进一步的机制研究表明，MAFB是RECQL 4的下游靶标。RECQL 4的致癌作用在MAFB敲低后减弱。此外，RECQL 4过表达受肿瘤抑制因子miR-10a-5 p负调控。总的来说，这些发现表明基因组扩增和miR-10a-5 p的低表达有助于卵巢癌中RECQL 4的过表达。这是首次揭示RECQL 4在卵巢癌中的致癌功能和临床意义的研究。
The high frequency of somatic copy number alterations, as opposed to point mutations, is considered a unique feature of ovarian cancer. Amplification-dependent overexpression of RecQ protein-like 4 (RECQL4), which participates in DNA replication and repair, mediates the development of various cancers, but its pathobiological and clinical roles are poorly understood. Here, using bioinformatics analysis, RECQL4 amplification was found to occur in 27% of ovarian cancer samples in the TCGA cohort. RECQL4 was found to be upregulated and associated with a poor prognosis based on the immunohistochemistry staining of ovarian cancer. Functionally, RECQL4 overexpression increased proliferation and invasion of ovarian cancer cells. RECQL4 silencing had the opposite effects. In addition, RECQL4 knockdown enhanced the sensitivity of ovarian cancer cells to cisplatin and PARP inhibitor (PARPi). Further mechanistic investigations revealed that MAFB was a downstream target of RECQL4. The oncogenic effect of RECQL4 was attenuated after MAFB knockdown. Moreover, RECQL4 overexpression was negatively regulated by the tumor suppressor miR-10a-5p. Collectively, these findings indicate that genomic amplification and low expression of miR-10a-5p contribute to RECQL4 overexpression in ovarian cancer. This is the first study to reveal the oncogenic functions and clinical significance of RECQL4 in ovarian cancer.
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影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
16.6
作者：
Labidi-Galy SI;Papp E;Hallberg D;Niknafs N;Adleff V;Noe M;Bhattacharya R;Novak M;Jones S;Phallen J;Hruban CA;Hirsch MS;Lin DI;Schwartz L;Maire CL;Tille JC;Bowden M;Ayhan A;Wood LD;Scharpf RB;Kurman R;Wang TL;Shih IM;Karchin R;Drapkin R;Velculescu VE
通讯作者：
Velculescu VE
RECQL4表达上调预示肝细胞癌预后不良
影响因子：
2.9
作者：
Li J;Jin J;Liao M;Dang W;Chen X;Wu Y;Liao W
通讯作者：
Liao W
影响因子：
4.7
作者：
Aziz, Diar;Etemadmoghadam, Dariush;Waring, Paul
通讯作者：
Waring, Paul
影响因子：
4.7
作者：
Shamanna, Raghavendra A.;Singh, Dharmendra Kumar;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.