H19 regulation of oestrogen induction of symmetric division is achieved by antagonizing Let-7c in breast cancer stem-like cells.
H19 regulation of oestrogen induction of symmetric division is achieved by antagonizing Let-7c in breast cancer stem-like cells.
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H19通过拮抗乳腺癌干细胞样细胞中的Let-7c来调节雌激素诱导对称分裂
DOI：
10.1111/cpr.12534
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发表时间：
2019-01
影响因子：
8.5
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Wang M;Li Y;Xiao GD;Zheng XQ;Wang JC;Xu CW;Qin S;Ren H;Tang SC;Sun X
乳腺癌干细胞样细胞（BrCSCs）是肿瘤产生、耐药和复发的主要原因。干细胞自我更新能力的紊乱有助于抑制干细胞的扩增。BrCSCs的分裂方式与其自我更新能力有关，对称分裂有助于提高其自我更新能力。H19的非编码长链RNA参与了多种恶性过程；H19的非编码长RNA在控制BrCSCs分裂中的作用和机制证明几乎不为人所知。采用TCGA数据库分析H19在临床前研究中的指示作用。荧光染色法确定细胞分裂方式。我们发现H19刺激BrCSCs的对称分裂，随后导致自我更新增加。H19作为其特异性分子海绵抑制了Let - 7c的可用性，通过抑制Let - 7c，雌激素受体激活的Wnt信号传导不受约束。同样，恢复Let‐7c抑制雌激素受体激活Wnt因子，从而抑制Let‐7生物利用度的H19降低。Let‐7c在体外被重新激活，H19被敲除，随后抑制BrCSCs的对称分裂。反过来，Wnt通路激活导致H19增加，从而降低Let - 7c的生物利用度。我们的研究结果揭示了先前未描述的海绵H19和靶向Let - 7c之间的双负反馈回路，通过雌激素激活Wnt信号传导，在干细胞分裂中占主导地位。
Breast cancer stem‐like cells (BrCSCs) are the major reason for tumour generation, resistance and recurrence. The turbulence of their self‐renewal ability could help to constrain the stem cell expansion. The way BrCSCs divided was related to their self‐renewal capacity, and the symmetric division contributed to a higher ability. Non‐coding long RNA of H19 was involved in multiple malignant procedures; the role and mechanistic proof of non‐coding long RNA of H19 in controlling the divisions of BrCSCs were barely known. Indicative functions of H19 in preclinical study were analysed by using the TCGA data base. Division manners were defined by using fluorescence staining. We identified the stimulation of H19 on symmetric division of BrCSCs, which subsequently resulted in self‐renewing increasing. H19 inhibited the Let‐7c availability by acting as its specific molecular sponge, and with Let‐7c inhibition, oestrogen receptor activated Wnt signalling was unconstrained. Similarly, restoring Let‐7c constrained oestrogen receptor activated Wnt factors, which sequentially inhibited the H19 decreasing of Let‐7 bioavailability. Let‐7c is reactivated in vitro where H19 was knockdown, and later inhibited the symmetric division of BrCSCs. Reciprocally, Wnt pathway activation leads to H19 increasing, which in turn decreased Let‐7c bioavailability. Our results revealed a previously undescribed double negative feedback loop between sponge H19 and targeted Let‐7c through oestrogen activated Wnt signalling that dominated in stem cells’ division.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
H19/let-7/LIN28相互负调节电路促进乳腺癌干细胞维持
影响因子：
9
作者：
Peng F;Li TT;Wang KL;Xiao GQ;Wang JH;Zhao HD;Kang ZJ;Fan WJ;Zhu LL;Li M;Cui B;Zheng FM;Wang HJ;Lam EW;Wang B;Xu J;Liu Q
通讯作者：
Liu Q
影响因子：
45.3
作者：
Kim, Chungyeul;Tang, Gong;Paik, Soonmyung
通讯作者：
Paik, Soonmyung
影响因子：
--
作者：
Sun X;Jiang S;Liu J;Wang H;Zhang Y;Tang SC;Wang J;Du N;Xu C;Wang C;Qin S;Zhang J;Liu D;Zhang Y;Li X;Wang J;Dong J;Wang X;Xu S;Tao Z;Xu F;Zhou J;Wang T;Ren H
通讯作者：
Ren H
影响因子：
4.7
作者：
Pine SR;Liu W
通讯作者：
Liu W