Potential new eye tumor treatment discovered

August 5, 2011

New research from a team including several Carnegie scientists demonstrates that a specific small segment of RNA could play a key role in the growth of a type of malignant childhood eye tumor called retinoblastoma. The tumor is associated with mutations of a protein called Rb, or retinoblastoma protein. Dysfunctional Rb is also involved with other types of cancers, including lung, brain, breast and bone. Their work, which will be the cover story of the August 15th issue of Genes & Development, could result in a new therapeutic target for treating this rare form of cancer and potentially other cancers as well.

MicroRNAs are a short, single strands of genetic material that bind to longer strands of messenger RNA--which is the courier that brings the genetic code from the DNA in the nucleus to the cell's ribosome, where it is translated into . This binding activity allows microRNAs to silence the expression of select in a targeted manner. Abnormal versions of microRNAs have been implicated in the growth of several types of cancer.

The paper from Carnegie's Karina Conkrite, Maggie Sundby and David MacPherson--as well as authors from other institutions—focuses on a cluster of microRNAs called miR-17~92. Recent research has shown that aberrant versions of this cluster are involved in preventing pre-cancerous cells from dying and allowing them to proliferate into tumors. Previous work has shown that miR-17~92 can be involved in the survival of lymphoma and leukemia cells by reducing the levels of a tumor-suppressing protein called PTEN.

The team's new research shows that miR-17~92 can also be involved in retinoblastoma, although it does not act in the same way, via the PTEN protein, as it does in other types of cancers. Rather, miR-17~92 acts to help cells that lack the tumor-suppressing Rb protein to proliferate.

First the team demonstrated that miR-17~92 is expressed in higher-than-usual quantities in all human retinoblastomas examined and in some mouse retinoblastomas. The authors engineered mice to express high levels of miR-17~92 in their retinas. When coupled with inactivation of Rb family members, expression of miR-17~92 led to extremely rapid and aggressive retinoblastoma. Then they showed that this abundance of miR-17~92 acts to suppress an inhibitor of proliferation, called p21Cip1, which is supposed to compensate for the loss of Rb.

"These findings— which show that miR-17~92 overcomes the cell's attempts to compensate for the loss of Rb—could be similar in other types of cancers," MacPherson said. "This microRNA cluster could represent a new therapeutic target for treating tumors caused by Rb deficiency."

Related Stories

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.