ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis.
ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis.
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DOI：
10.1038/s41419-021-04256-9
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发表时间：
2021-12-09
影响因子：
9
通讯作者：
Jia W
中科院分区：
文献类型：
--
作者：
Liu P;Fu R;Chen K;Zhang L;Wang S;Liang W;Zou H;Tao L;Jia W
高级别浆液性卵巢癌（HGSOC）是女性生殖系统常见的致命性癌症。长链非编码RNA（lncRNA）在多种癌症中异常表达，并在肿瘤进展中起关键作用。然而，它们在HGSOC中的功能和分子机制在很大程度上仍然未知。基于公共数据库和生物信息学分析，在HGSOC组织中检测并验证了lncRNA CTBP 1-DT在HGSOC组织中的过表达。lncRNA CTBP 1-DT的高表达与不良预后相关，并且是生存的独立危险因素。通过体外和体内实验，lncRNA CTBP 1-DT的过表达促进了HGSOC细胞的恶性生物学行为，而其缺失诱导了HGSOC细胞的生长停滞。在机制上，lncRNA CTBP 1-DT可以竞争性结合miR-188- 5 p以保护MAP 3 K3免于降解。此外，我们的研究结果表明，ETV 5可以特异性地与lncRNA CTBP 1-DT的启动子相互作用，并激活其转录。总的来说，这些结果揭示了HGSOC进展的新ETV 5/lncRNA CTBP 1-DT/miR-188- 5 p/MAP 3 K3途径，并表明lncRNA CTBP 1-DT可能是HGSOC的潜在生物标志物和治疗靶标。
High-grade serous ovarian cancer (HGSOC) is a common and lethal cancer of the female reproductive system. Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers and play crucial roles in tumour progression. However, their function and molecular mechanism in HGSOC remain largely unknown. Based on public databases and bioinformatics analyses, the overexpression of lncRNA CTBP1-DT in HGSOC tissues was detected and validated in a cohort of HGSOC tissues. High expression of lncRNA CTBP1-DT was associated with poor prognosis and was an independent risk factor for survival. Overexpression of lncRNA CTBP1-DT promoted malignant biological behaviour of HGSOC cells, whereas its depletion induced growth arrest of HGSOC cells by vitro and in vivo assays. Mechanistically, lncRNA CTBP1-DT could competitively bind to miR-188-5p to protect MAP3K3 from degradation. Moreover, our results revealed that ETV5 could specifically interact with the promoter of lncRNA CTBP1-DT and activate its transcription. Collectively, these results reveal a novel ETV5/lncRNA CTBP1-DT/miR-188-5p/MAP3K3 pathway for HGSOC progression and suggest that lncRNA CTBP1-DT might be a potential biomarker and therapeutic target for HGSOC.
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影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
DOI：
10.1097/gme.0000000000001655
发表时间：
2020-11-01
期刊：
MENOPAUSE-THE JOURNAL OF THE MENOPAUSE SOCIETY
影响因子：
--
作者：
Si, Lihui;Chen, Jun;Jia, Yan
通讯作者：
Jia, Yan
STAT3诱导的lncRNA HAGLROS过表达通过mTOR信号介导的自噬抑制促进胃癌细胞的恶性进展
影响因子：
37.3
作者：
Chen JF;Wu P;Xia R;Yang J;Huo XY;Gu DY;Tang CJ;De W;Yang F
通讯作者：
Yang F
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
4
作者：
Cui, Kaiying;Zhu, Genhai
通讯作者：
Zhu, Genhai