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Angiogenesis

, Volume 22, Issue 2, pp 251–262 | Cite as

The regulatory network of miR-141 in the inhibition of angiogenesis

  • Haojie Dong
  • Chunhua Weng
  • Rongpan Bai
  • Jinghao Sheng
  • Xiangwei Gao
  • Ling Li
  • Zhengping XuEmail author
Original Paper

Abstract

The miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models. Particularly, the effect of miR-141 in vascular endothelial cells has not been defined. In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis. Additional mechanistic studies showed that miR-141 suppresses angiogenesis through multiple targets, including NRP1, GAB1, CXCL12β, TGFβ2, and GATA6, and bioinformatics analysis indicated that miR-141 and its targets comprise a powerful and precise regulatory network to modulate angiogenesis. Taken together, these data not only demonstrate an anti-angiogenic effect of miR-141, further strengthening the critical role of miR-200 family in the process of angiogenesis, but also provides a valuable cancer therapeutic target to control both angiogenesis and EMT, two essential steps in tumor growth and metastasis.

Keywords

miR-141 miR-200 family Angiogenesis Regulatory network 

Notes

Acknowledgements

We appreciate Dr. Kerin Higa (City of Hope) and Dr. Wen Jin (Sigilon therapeutics) for critically reading the manuscript and for helpful discussions. This work was supported by the grants from the National Natural Science Foundation of China [Grant Numbers 31570786, 31600630 and 31770867] and the China Postdoctoral Science Foundation China [Grant Number 2016M591990].

Supplementary material

10456_2018_9654_MOESM1_ESM.pptx (3.8 mb)
Supplementary Figures 1 (PPTX 3857 KB)
10456_2018_9654_MOESM2_ESM.pptx (461 kb)
Supplementary Tables 2 (PPTX 461 KB)
10456_2018_9654_MOESM3_ESM.docx (23 kb)
Supplementary material 3 (DOCX 23 KB)

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Institute of Environmental Medicine, and Cancer Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesZhejiang UniversityHangzhouChina
  3. 3.Program in Molecular and Cellular BiologyZhejiang University School of MedicineHangzhouChina
  4. 4.Department of Hematological Malignancies Translational Science, Beckman Research InstituteCity of Hope Medical CenterDuarteUSA
  5. 5.Kidney Disease Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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