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STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.


ABSTRACT: Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

SUBMITTER: Pan S 

PROVIDER: S-EPMC7791041 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

Pan Shunli S   Zhao Xiaoxia X   Shao Chen C   Fu Bingjie B   Huang Yingying Y   Zhang Ning N   Dou Xiaojing X   Zhang Zhe Z   Qiu Yuling Y   Wang Ran R   Jin Meihua M   Kong Dexin D  

Cell death & disease 20210104 1


Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca<sup>2+</sup>. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca<sup>2+</sup> signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF  ...[more]

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