A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability.
A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability.
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一种新型低氧长非编码 RNA KB-1980E6.3 通过与 IGF2BP1 相互作用促进 c-Myc mRNA 稳定性来维持乳腺癌干细胞干细胞性
DOI：
10.1038/s41388-020-01638-9
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发表时间：
2021-03
期刊：
影响因子：
8
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Zhu P;He F;Hou Y;Tu G;Li Q;Jin T;Zeng H;Qin Y;Wan X;Qiao Y;Qiu Y;Teng Y;Liu M
恶劣的缺氧微环境是乳腺癌肿瘤快速扩张的主要原因。然而，其基本机制尚未完全了解。在这里，使用RNA测序（RNA-seq）分析，我们鉴定了缺氧诱导的长非编码RNA（lncRNA）KB-1980E6.3，其在临床乳腺癌组织中异常上调，并且与乳腺癌患者的不良预后密切相关。增强的lncRNA KB-1980E6.3在体外和体内促进乳腺癌干细胞（BCSC）在缺氧微环境下的自我更新和肿瘤发生。从机制上讲，lncRNA KB-1980 E6.3募集胰岛素样生长因子2 mRNA结合蛋白1（IGF 2BP 1）形成lncRNA KB-1980 E6.3/IGF 2BP 1/c-Myc信号轴，通过增加IGF 2BP 1与m6 A修饰的c-Myc编码区不稳定决定簇（CRD）mRNA的结合来保持c-Myc mRNA的稳定性。总之，我们证实lncRNA KB-1980E6.3通过lncRNA KB-1980E6.3/IGF 2BP 1/c-Myc轴维持BCSC的干性，并表明破坏该轴可能为难治性缺氧肿瘤提供新的治疗靶点。
The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.
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影响因子：
30.8
作者：
Bhandari, Vinayak;Hoey, Christianne;Bristow, Robert G.
通讯作者：
Bristow, Robert G.
影响因子：
20.3
作者：
Bueno, Mara J.;Gomez de Cedron, Marta;Malumbres, Marcos
通讯作者：
Malumbres, Marcos
影响因子：
16
作者：
Lal A;Navarro F;Maher CA;Maliszewski LE;Yan N;O'Day E;Chowdhury D;Dykxhoorn DM;Tsai P;Hofmann O;Becker KG;Gorospe M;Hide W;Lieberman J
通讯作者：
Lieberman J
影响因子：
8
作者：
Bell, Jessica L.;Waechter, Kristin;Muehleck, Britta;Pazaitis, Nikolaos;Koehn, Marcel;Lederer, Marcell;Huettelmaier, Stefan
通讯作者：
Huettelmaier, Stefan
影响因子：
11.2
作者：
Adinolfi, Elena;Raffaghello, Lizzia;Di Virgilio, Francesco
通讯作者：
Di Virgilio, Francesco