Related Experiment Video

Updated: Mar 13, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

8.1K

A MicroRNA302-367-Erk1/2-Klf2-S1pr1 Pathway Prevents Tumor Growth via Restricting Angiogenesis and Improving Vascular

Jingjiang Pi1, Ting Tao1, Tao Zhuang1

  • 1From the Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, China (J.P., T.Z., H.S., X.C., J.L., Z.Y., L.Z., Y.Z.); Department of Geriatrics, Ruijin Hospital, School of Medicine (T.T.) and State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, (Y.S., X.W.), Shanghai Jiao Tong University, China; Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai, China (Y.C.); Med-X-Renji Hospital Stem Cell Research Center, Jiao Tong University School of Medicine, Shanghai, China (H.H.Z., W.-Q.G.); Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan (P.C.); Laboratory of Cardiovascular Signaling, Centenary Institute, Camperdown, New South Wales, Australia (X.Z.); Department of Medicine, Sydney Medical School, University of Sydney, New South Wales, Australia (X.Z.); Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (Y.T.); and Department of Cell and Developmental Biology, Department of Medicine, Penn Cardiovascular Institute, Penn Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia (E.M.).

Circulation Research
|October 21, 2016
PubMed
Abstract

Insights

MicroRNA 302-367 cluster inhibits blood vessel growth and enhances stability by targeting Erk1/2, Klf2, and S1pr1 pathways. This discovery offers new therapeutic strategies for controlling tumor growth and related diseases.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • Tumor growth relies on new blood vessel formation (angiogenesis) characterized by excessive sprouting and leaky vessels.
  • MicroRNAs offer therapeutic potential for angiogenesis by targeting multiple pathways, but the miR302-367 cluster's specific roles remain unclear.

Purpose of the Study:

  • To investigate the function of the miR302-367 cluster in both developmental and tumor angiogenesis.
  • To elucidate the molecular mechanisms underlying microRNA-mediated regulation of pathological neovascularization.

Main Methods:

  • In vivo, ex vivo, and in vitro studies using endothelial cells.
  • Identification of direct targets of miR302-367, including Erk1/2.
  • Analysis of downstream signaling pathways (Klf2, S1pr1, VE-cadherin) and pharmacological/genetic manipulation of S1pr1.

Main Results:

  • Elevated miR302-367 in endothelial cells reduced retinal angiogenesis and improved vascular stability.
  • miR302-367 directly targets Erk1/2, leading to increased Klf2 and S1pr1 expression, suppressing angiogenesis.
  • Endothelial-specific miR302-367 elevation reduced tumor growth by inhibiting angiogenesis and vascular permeability via the Erk1/2-Klf2-S1pr1 pathway.

Conclusions:

  • MiR302-367 plays a critical role in regulating angiogenesis through the Erk1/2-Klf2-S1pr1 pathway in endothelial cells.
  • This pathway presents a novel therapeutic target for inhibiting tumor growth and treating diseases associated with pathological neovascularization.
Keywords:
angiogenesisblood vessel tumorendothelial cellsmicroRNAs

More Related Videos

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

10.2K
Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma13:18

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

1.8K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.9K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.1K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
7.4K