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.

• Authors: Shunli Pan, Xiaoxia Zhao, Chen Shao, Bingjie Fu, Yingying Huang, Ning Zhang, Xiaojing Dou, Zhe Zhang, Yuling Qiu, Ran Wang, Meihua Jin, Dexin Kong
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 1 Pg. 38 (01 04 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 33414420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN145 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• STIM1 protein, human
• Stromal Interaction Molecule 1

Topics

• Animals
• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Exosomes (metabolism)
• Female
• Human Umbilical Vein Endothelial Cells
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (metabolism)
• Neoplasm Proteins (physiology)
• Neovascularization, Pathologic (metabolism)
• Stromal Interaction Molecule 1 (physiology)