MicroRNA molecules entering a cell through a NRP1 receptor.

Cell Communication Unlocked: How miRNAs and NRP1 Could Revolutionize Cancer Treatment

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Nico Varela in Health & Wellness December 2025 • 4 min read.

"Discover the groundbreaking research on how neuropilin-1 (NRP1) acts as a key receptor for microRNAs, potentially transforming our approach to cancer therapy."


Extracellular miRNAs are emerging as significant markers in various diseases, exhibiting remarkable stability in biological fluids. These tiny molecules play a vital role in intercellular communication, protected from degradation either through encapsulation in microparticles or by binding to proteins like AGO2. Understanding how these protected miRNAs are taken up by cells is crucial.

While encapsulated miRNAs may enter cells via endocytosis or membrane fusion, protein-bound miRNAs require a receptor mechanism for cellular uptake. The central question researchers are now asking is: do natural cell-membrane receptors exist that capture and internalize protein-bound, functional miRNAs? This search led researchers to explore neuropilin-1 (NRP1).

Neuropilin-1 (NRP1) is a receptor known for binding to various ligands, including vascular endothelial growth factor (VEGF). It's highly efficient at mediating ligand internalization and is expressed in endothelial, normal, and cancer cells, making it a prime candidate for miRNA uptake. This article delves into the groundbreaking research demonstrating NRP1's ability to bind and internalize miRNAs, opening new avenues for cancer therapy.

How NRP1 Acts as a Gateway for miRNAs

MicroRNA molecules entering a cell through a NRP1 receptor.

Researchers have discovered that NRP1 acts as a high-affinity receptor for miRNAs, facilitating their entry into cells. This process is crucial because the miRNAs, once inside, maintain their functionality, influencing key cellular processes such as proliferation, migration, and tube formation in endothelial cells. These findings highlight NRP1's significant role in mediating miRNA uptake and function.

Further experiments using anti-NRP1 antibodies and siRNA knockdown techniques confirmed that NRP1 is indeed essential for miRNA uptake. Blocking NRP1 function effectively inhibited miRNA effects, underscoring the receptor's specificity. Notably, VEGF, another known ligand of NRP1, did not compete with miRNAs for binding, suggesting a distinct interaction mechanism.

Here are the key ways NRP1 facilitates miRNA's role:
  • High Affinity Binding: NRP1 binds miRNAs with high affinity, initiating the internalization process.
  • Functional Impact: Once internalized, miRNAs regulate critical cellular functions like proliferation and migration.
  • Specificity: Anti-NRP1 antibodies and siRNA confirm NRP1's role in miRNA uptake.
  • Distinct Mechanism: VEGF does not compete with miRNAs for NRP1 binding.
Adding another layer of complexity, the study revealed that NRP1 also binds extracellular AGO2, a protein known to carry miRNAs. This binding allows NRP1 to internalize AGO2/miRNA complexes, a significant finding given that miRNAs bound to AGO2 are the most abundant form in body fluids. This mechanism suggests that NRP1 plays a crucial role in how cells respond to circulating miRNAs, with broad implications for both physiological and pathological processes.

Implications and Future Directions

This research illuminates the critical role of NRP1 in capturing and internalizing miRNAs and AGO2/miRNA complexes, which influences cell behavior. Targeting intercellular communication mechanisms offers promising avenues for cancer therapy, presenting an opportunity to modulate tumor growth, metastasis, and immune responses.

Further research is needed to fully elucidate the intricacies of NRP1-mediated miRNA uptake. Identifying specific miRNA targets and how they influence cellular processes will pave the way for developing targeted therapies. Future investigations should explore the structural aspects of the NRP1-miRNA interaction and the specific signaling pathways involved.

By unlocking the mechanisms of miRNA signaling, we can develop innovative therapeutic strategies that precisely target cancer cells while sparing healthy tissue. This could lead to a new era of personalized medicine, with treatments tailored to the unique miRNA profiles of individual tumors, enhancing efficacy and minimizing side effects.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.18632/oncotarget.10929, Alternate LINK

Title: Neuropilin-1 Is A Receptor For Extracellular Mirna And Ago2/Mirna Complexes And Mediates The Internalization Of Mirnas That Modulate Cell Function

Subject: Oncology

Journal: Oncotarget

Publisher: Impact Journals, LLC

Authors: Gerald J. Prud’Homme, Yelena Glinka, Zsuzsanna Lichner, George M. Yousef

Published: 2016-07-29

Everything You Need To Know

1

What is the role of Neuropilin-1 (NRP1) in cell communication and how does it work?

Neuropilin-1 (NRP1) is a receptor that acts as a gateway for microRNAs (miRNAs) to enter cells. Researchers have found that NRP1 binds to miRNAs with high affinity, allowing them to be internalized. This process is critical because once inside the cell, the miRNAs can influence key cellular functions like proliferation, migration, and tube formation, making NRP1's role in cancer therapy highly significant.

2

What are microRNAs (miRNAs), and why are they important for cell function?

miRNAs are small molecules that play a key role in communication between cells. They are often protected from degradation, either by being enclosed in microparticles or by binding to proteins like AGO2. Extracellular miRNAs are stable in biological fluids, and understanding how these miRNAs are taken up by cells is vital for understanding cell behavior in both normal and diseased states. The internalization process of these miRNAs directly impacts cell function.

3

Why is Neuropilin-1 (NRP1) important in the context of cancer treatment?

The significance of NRP1 in cancer treatment lies in its ability to mediate the uptake of miRNAs, which can influence cancer cell behavior. By targeting NRP1, it may be possible to modulate tumor growth, metastasis, and immune responses. The discovery that NRP1 can bind and internalize miRNAs and AGO2/miRNA complexes opens new possibilities for cancer therapy. Because miRNAs regulate cellular processes, targeting NRP1 could provide new ways to combat cancer.

4

How does NRP1 differ from other cell-membrane receptors in its function?

The difference between NRP1 and other cell-membrane receptors is the specificity of its binding mechanism. NRP1 uniquely binds and internalizes miRNAs. Unlike other known ligands for NRP1, such as VEGF, the binding of miRNAs to NRP1 occurs via a distinct mechanism. This high-affinity binding initiates the internalization process, allowing miRNAs to regulate critical cellular functions. This specificity allows for a targeted approach to disrupting cell signaling pathways in cancer cells.

5

What are the implications of this research, and what future directions does it suggest?

The research suggests several future directions. Targeting NRP1 could provide a new avenue for cancer therapy. The discovery of NRP1's role in capturing and internalizing miRNAs and AGO2/miRNA complexes presents an opportunity to modulate tumor growth, metastasis, and immune responses. Further research could investigate the specific miRNAs involved, and the mechanisms by which they affect cellular processes. The goal is to use this understanding to develop novel cancer treatments.

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