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MicroRNA

Using MicroRNA to Starve a Tumor?

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Endothelial cells are inhibited from sprouting
Credit: Dudley Lab, University of Virginia School of Medicine, Charlottesville

Tumor cells thrive by exploiting the willingness of normal cells in their neighborhood to act as accomplices. One of their sneakier stunts involves tricking the body into helping them form new blood vessels. This growth-enabling process of sprouting new blood vessels, called tumor angiogenesis, remains a vital area of cancer research and continues to yield important clues into how to beat this deadly disease.

The two-panel image above shows one such promising lead from recent lab studies with endothelial cells, specialized cells that line the inside of all blood vessels. In tumors, endothelial cells are induced to issue non-stop SOS signals that falsely alert the body to dispatch needed materials to rescue these cells. The endothelial cells then use the help to replicate and sprout new blood vessels.

The left panel demonstrates the basics of this growth process under normal conditions. Endothelial cells (red and blue) were cultured under special conditions that help them grow in the lab. When given the right cues, those cells sprout spiky extensions to form new vessels.

But in the right panel, the cells can’t sprout. The reason is because the cells are bathed in a molecule called miR-30c, which isn’t visible in the photo. These specialized microRNA molecules—and humans make a few thousand different versions of them—control protein production by binding to and disabling longer RNA templates, called messenger RNA.

This new anti-angiogenic lead, published in the Journal of Clinical Investigation, comes from a research team led by Andrew Dudley, University of Virginia Medical School, Charlottesville [1]. The team made its discovery while studying a protein called TGF-beta that tumors like to exploit to fuel their growth.

Their studies in mice showed that loss of TGF-beta signals in endothelial cells blocked the growth of new blood vessels and thus tumors. Further study showed that those effects were due in part to elevated levels of miR-30c. The two interact in endothelial cells as part of a previously unrecognized signaling pathway that coordinates the growth of new blood vessels in tumors.

Dudley’s team went on to show that levels of miR-30c vary widely amongst endothelial cells, even when those cells come from the very same tumor. Cells rich in miR-30c struggled to sprout new vessels, while those with less of this microRNA grew new vessels with ease.

Intriguingly, they found that levels of this microRNA also predicted the outcomes for patients with breast cancer. Those whose cancers had high levels of the vessel-stunting miR-30c fared better than those with lower miR-30c levels. While more research is needed, it does offer a potentially promising new lead in the fight against cancer.

Reference:

[1] Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β-induced Serpine1. McCann JV, Xiao L, Kim DJ, Khan OF, Kowalski PS, Anderson DG, Pecot CV, Azam SH, Parker JS, Tsai YS, Wolberg AS, Turner SD, Tatsumi K, Mackman N, Dudley AC. J Clin Invest. 2019 Mar 11;130:1654-1670.

Links:

Angiogenesis Inhibitors (National Cancer Institute/NIH)

Dudley Lab (University of Virginia School of Medicine, Charlottesville)

NIH Support: National Cancer Institute; National Heart, Lung, and Blood Institute


Researchers Elucidate Role of Stress Gene in Chronic Pain

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Credit: Getty Images/simonkr

For most people, pain eventually fades away as an injury heals. But for others, the pain persists beyond the initial healing and becomes chronic, hanging on for weeks, months, or even years. Now, we may have uncovered an answer to help explain why: subtle differences in a gene that controls how the body responds to stress.

In a recent study of more than 1,600 people injured in traffic accidents, researchers discovered that individuals with a certain variant in a stress-controlling gene, called FKBP5, were more likely to develop chronic pain than those with other variants [1]. These findings may point to new non-addictive strategies for preventing or controlling chronic pain, and underscore the importance of NIH-funded research for tackling our nation’s opioid overuse crisis.


MicroRNA Research Takes Aim at Cholesterol

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Illustration of artery partially blocked by a cholesterol plaque

Caption: Illustration of artery partially blocked by a cholesterol plaque.

If you’re concerned about your cardiovascular health, you’re probably familiar with “good” and “bad” cholesterol: high-density lipoprotein (HDL) and its evil counterpart, low-density lipoprotein (LDL). Too much LDL floating around in your blood causes problems by sticking to the artery walls, narrowing the passage and raising risk of a stroke or heart attack. Statins work to lower LDL. HDL, on the other hand, cruises through your arteries scavenging excess cholesterol and returning it to the liver, where it’s broken down.


exRNA: Helping Cells Get Their Message Out

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DNA helix surrounded by a bubble.

Caption: exRNA enveloped in a fatty bubble transmits messages between cells. Click here to view the video.
Source: NIH Common Fund

When your email is interrupted or blocked, it creates havoc. Messages remain undelivered, stalling interactions between you and your friends, family, and colleagues at work. Likewise when communication fails between your body’s cells, disease can result. Scientists recently discovered a new group of molecules called extracellular RNA (exRNA) that appears to travel between cells to help them communicate. Now, NIH is encouraging researchers to explore the potential of these newly discovered messengers.