MicroRNA cooperation mutes breast cancer oncogenes

May 7, 2013

A University of Colorado Cancer Center study recently published in the journal Cell Death & Disease shows that turning up a few microRNAs a little may offer as much anti-breast-cancer activity as turning up one microRNA a lot – and without the unwanted side effects.

It's a bit like the classic thought experiment known as the "tumor problem" formulated by Karl Dunker in 1945 and used frequently in the problem-solving literature: Imagine a person suffers from a malignant tumor in the center of her body. Radiation strong enough to kill the tumor kills any healthy tissue through which it passes. Without operating or killing healthy tissue, how can a doctor use radiation to kill the tumor?

The answer is to target the tumor from many angles – many weak rays of radiation pass harmlessly through healthy tissue, but their combined power at the point of the tumor is enough to kill it.

In the present study, CU Cancer Center investigators used "weak" induction of multiple microRNAs that combined from many angles to regulate the known breast cancer oncogenes erbB2/erbB3 (the "") without regulating non-target genes (the "healthy tissue").

"Imagine you have a microRNA that regulates genes A and B. Then you have another microRNA that regulates genes B and C. You amplify each microRNA to a degree that doesn't effect gene A or C, but their combined effect regulates gene B," says Bolin Liu, MD, assistant professor in the Department of Pathology at the University of Colorado School of Medicine.

microRNA is an attractive target in cancer therapy – more microRNA can lead to less gene expression, turning down or off the oncogenes that cause cancer. However, to get the desired effect on gene expression frequently requires enhancing microRNA expression 100- or 1,000-fold (or more). And the induced microRNA likely has other genetic targets – it will turn down other genes as well as the oncogene, sometimes with unfortunate consequences.

"The current study showed that two microRNAs enhanced only 3-to-6 times their natural expression could cooperate to regulate an oncogene that had previously only been affected by a microRNA enhanced by many, many times this amount," Liu says.

Specifically, the group's work shows that no one alone, but any two of the three microRNAs that regulate erbB2/erbB3 expression can affect the levels of proteins produced by the genes. These are miR-125a, miR-15b, and miR-205, which act in concert to regulate the expression of erbB2/erbB3, which are -causing products of the oncogenes.

But in general, the group's novel technique could have implications far past erbB2/erbB3, allowing researchers and eventually doctors to mute the genes they want to mute without also dampening the expression of regulated by only one or only the other microRNA partner.

Explore further: MicroRNA-218 targets medulloblastoma, most aggressive childhood brain cancer

Related Stories

MicroRNA-218 targets medulloblastoma, most aggressive childhood brain cancer

December 13, 2012
Between the blueprint of the genome and the products of its expression lie microRNAs, which can boost or lower the rate at which genes become stuff. In fact, many cancers use microRNA to magnify the expression of faulty genes ...

Serendipity points to new potential target and therapy for melanoma

December 20, 2012
(Medical Xpress)—A University of Colorado Cancer Center study in this month's edition of the Journal of Investigative Dermatology describes a new target and potential treatment for melanoma, the most dangerous form of skin ...

Small molecules shed light on cancer therapies

August 22, 2011
Patients suffering from an aggressive brain cancer will benefit from the results of a University of Illinois study that could advance the development of targeted gene therapies and improve prognosis.

Recommended for you

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.