miRNA replacement based cancer therapies

November 30, 2020

Mrs. Anukriti Singh is currently a PhD student in the lab of Prof. Bushra Ateeq (Shanti Swarup Bhatnagar Prize 2020 for Medical Sciences) at the Department of Biological Sciences & Bioengineering, Indian Institute of Technology, Kanpur. She published a paper titled “Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma” as the first author in Neoplasia (2020).

Author Interview

How would you explain your paper’s key results to the non-scientific community?

AGTR1 is a gene known for regulating blood pressure, but when overexpressed, it acts as an oncogene (cancer-causing gene) in organs like the brain and breast. The mechanism behind its overexpression in cancer was previously unclear. Our study uncovered that AGTR1-driven cancers, including glioblastoma (GBM) and breast cancer (BCa), are fueled by a signaling cascade involving:

The Angiotensin II ligand activating the AGTR1 receptor
This triggers the NF-κB pathway
Which in turn activates another gene, CXCR4
CXCR4 then upregulates AGTR1 via a feedback loop

This AGTR1/NF-κB/CXCR4 axis sustains cancer progression.

We found that microRNA-155 (miR-155), a small RNA molecule, can disrupt this signaling axis. miR-155 blocks AGTR1 overexpression, inhibits tumor-promoting functions like blood vessel formation (angiogenesis), cell growth, and invasion in GBM and BCa cells. Strikingly, in mouse models, GBM cells with miR-155 failed to form tumors, while control cells did.

We also showed that IKK inhibitors—drugs targeting NF-κB—can suppress this axis. Thus, our research suggests miRNA therapy and IKK inhibitors as promising treatments for AGTR1-positive cancers.

“We propose a therapeutic intervention for AGTR1-positive cancer patients through miRNA replacement therapy and IKK inhibitors.”

What are the possible consequences of these findings for your research area?

GBM is one of the deadliest brain cancers, with survival averaging 15 months (with treatment). Breast cancer is the most diagnosed cancer in women in India and globally. Our research offers a targeted therapy approach for AGTR1-positive patients with GBM and BCa using:

miRNA replacement therapy
IKK pathway inhibitors

Both approaches are currently in clinical trials for other diseases, including strategies for delivering miRNAs across the blood-brain barrier. Therefore, our findings hold strong translational potential.

What was the exciting moment (eureka moment) during your research?

Quoting Einstein: “To raise new questions, new possibilities, to regard old problems from a new angle, requires creative imagination and marks real advance in science.”

The most exciting moment came when GBM cells overexpressing miR-155 failed to grow tumors in mice—an outcome clearly visible to the naked eye. This encouraged us to explore the pathways involved, eventually discovering the AGTR1/NF-κB/CXCR4 axis. Each piece of this pathway, uncovered step-by-step, brought its own eureka moment.

What do you hope to do next?

The next logical step is to develop delivery methods for these miRNAs in vivo and push miRNA replacement therapy toward clinical trials.

Where do you seek scientific inspiration?

From the start, I’ve been drawn to translational research—especially disease research involving real patients. Interacting with patients facing tough battles motivated me to contribute to disease-focused science. My inspiration comes from wanting to make a meaningful difference in patients’ lives, however small.

How do you intend to help Indian science improve?

Indian science is growing rapidly, but much of its lab research doesn’t reach clinical application. I aim to bridge that gap—bringing research from bench to bedside to help patients benefit from scientific discoveries.

Reference

Singh A, Srivastava N, Yadav A, Ateeq B.
Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma. Neoplasia. 2020;22(10):497-510.

Learn More

🔬 Prof. Bushra Ateeq’s Lab Research
📰 Scisoup article on the findings
🎥 Watch Anukriti’s video summary

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