STARD13-correlated ceRNA network-directed inhibition on YAP/TAZ activity suppresses stemness of breast cancer via co-regulating Hippo and Rho-GTPase/F-actin signaling.
STARD13-correlated ceRNA network-directed inhibition on YAP/TAZ activity suppresses stemness of breast cancer via co-regulating Hippo and Rho-GTPase/F-actin signaling.
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STARD13相关的ceRNA网络定向抑制YAP/TAZ活性通过共同调节Hippo和Rho-GTPase/F-actin信号传导抑制乳腺癌的干性
DOI：
10.1186/s13045-018-0613-5
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发表时间：
2018-05-30
影响因子：
28.5
通讯作者：
Xi T
中科院分区：
文献类型：
--
作者：
Zheng L;Xiang C;Li X;Guo Q;Gao L;Ni H;Xia Y;Xi T
靶向癌症干细胞是抑制癌症进展和复发的关键。寻找新的标志物或相关途径有助于临床根除或诊断癌症。通过构建stard13相关的ceRNA 3'UTR稳定过表达或敲低的乳腺癌细胞，我们旨在探讨stard13相关的ceRNA网络对乳腺癌干细胞的体外和体内影响。进一步的rna测序结合候选信号的功能研究来分析转录组变化。从癌症基因组图谱数据中获得的临床样本用于验证STARD13与相关途径之间的相关性。最后，通过体外和体内实验，研究stard13相关的ceRNA网络对化疗敏感性/耐药的影响。在这里，我们发现这个ceRNA网络抑制乳腺癌的干性。在机制上，我们发现stard13相关的ceRNA网络的激活与乳腺癌中YAP/TAZ的活性呈负相关。具体来说，该ceRNA网络通过集体调节Hippo和Rho-GTPase/F-actin信号传导，减弱了YAP/TAZ核积累和转录活性。最后，我们证明了受该ceRNA网络调控的YAP/TAZ转录活性参与了化学耐药。我们的研究结果揭示了乳腺癌中YAP/TAZ激活的新机制，并提出了驱动stard13相关的ceRNA网络抑制乳腺癌干细胞特性的可能性。本文的在线版本（10.1186/s13045-018-0613-5）包含补充内容，仅供授权用户使用。
Targeting cancer stem cells is critical for suppressing cancer progression and recurrence. Finding novel markers or related pathways could help eradicate or diagnose cancer in clinic. By constructing STARD13-correlated ceRNA 3′UTR stable overexpression or knockdown breast cancer cells, we aimed to explore the effects of STARD13-correlated ceRNA network on breast cancer stemness in vitro and in vivo. Further RNA-sequencing was used to analyze transcriptome change in combination with functional studies on candidate signaling. Clinical samples obtained from The Cancer Genome Atlas data were used to validate the correlation between STARD13 and related pathways. Finally, in vitro and in vivo experiments were used to examine the effects of STARD13-correlated ceRNA network on chemotherapy sensitivity/resistance. Here, we revealed that this ceRNA network inhibited stemness of breast cancer. Mechanistically, we found that activation of STARD13-correlated ceRNA network was negatively correlated with YAP/TAZ activity in breast cancer. Specifically, this ceRNA network attenuated YAP/TAZ nuclear accumulation and transcriptional activity via collectively modulating Hippo and Rho-GTPase/F-actin signaling. Finally, we demonstrated that YAP/TAZ transcriptional activity regulated by this ceRNA network was involved in chemoresistance. Our results uncover a novel mechanism of YAP/TAZ activation in breast cancer and propose the possibility to drive STARD13-correlated ceRNA network to inhibit breast cancer stem cell traits. The online version of this article (10.1186/s13045-018-0613-5) contains supplementary material, which is available to authorized users.
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