Navigation Links
Single microRNA causes cancer in transgenic mouse

Scientists in the Ohio State University Comprehensive Cancer Center say that just one, single, malfunctioning microRNA is sufficient to cause cancer in mice. The discovery offers new insight into the development of some forms of leukemia and lymphoma and at the same time underscores the powerful role that these tiny snippets of non-coding RNA play in cell signaling pathways active in carcinogenesis.

"To the best of our knowledge, this is the first direct evidence that overexpression of a microRNA results in the development of a neoplastic disease, highlighting their potential role in human malignancies," says Carlo Croce, director of Ohio State's Human Cancer Genetics Program and professor and chair of the department of molecular virology, immunology and medical genetics.

Over the past several years, scientists have discovered hundreds of microRNAs (miRNAs) and how they regulate gene expression ?basically, by blocking messenger RNA's instructions for protein production. MiRNAs normally help control important biological functions by switching "on" and "off" at different times during cell growth, death, development and differentiation. They can be harmful, though, if they are activated at the wrong time in the wrong place, and that appears to be what happens in some forms of cancer.

The study is published online in the Proceedings of the National Academy of Sciences.

Croce, the senior author of the study and the first to identify a link between miRNAs and cancer, suspected that a particular miRNA, miR155, was a key culprit in some forms of malignant growth. He and his colleagues have been mapping the activity of dozens of miRNAs in various types of normal and malignant tissues for several years. Earlier studies showed that miR155 was unusually active in some types of leukemia and lymphoma, and that its presence indicated a poorer prognosis in patients with breast and lung cancers.

Croce, along with Dr. Stefan Costinean , a r esearch associate, decided to isolate miR155 function by inserting the gene, along with an enhancer, to promote its expression, into fertilized eggs inside a pregnant mouse. The researchers then screened the offspring to find those that had incorporated miR155 into their genomes and followed them to see what effect miR155 might have.

Within three weeks, the transgenic mice developed greatly enlarged spleens, and after six to seven months, they became sick and died. Offspring that did not express miR 155 did not have enlarged spleens and developed normally.

When Costinean examined the spleens of the transgenic mice more closely, he discovered they were full of immature B cells ?and only immature B cells.

"This is significant, because a proliferation of these precursor B cells is one of the hallmarks of some types of leukemia and lymphoma," he said.

B cells, or lymphocytes, are white blood cells that help the body fight infection.

In humans, they are produced from stem cells in the bone marrow and then evolve through several stages before they become mature enough to create antibodies. Antibodies are proteins that sit on the surface of B cells or that are secreted by B cells that can detect the presence of foreign invaders like bacteria, viruses or parasites.

Lab tests revealed that the B cells in enlarged spleens had stopped evolving in the pre-B phase, right at the point where a B cell normally begins to create structures necessary for antibody development.

"We believe that miR 155 initiated the process that blocked further differentiation of these cells," says Costinean.

Croce says the results are consistent with previous study findings. "We know that miRNAs often act just like oncogenes, in that they promote abnormal cell growth that leads to cancer. Others, however, behave more like tumor suppressors, because they block genes that keep abnormal cell division in check or induce prolonged survi val. Our transgenic mouse model clearly shows that miR155 is an oncogene, because it leads to B cell malignancies when it is dysregulated."

Although they now understand that miR 155 overexpression can lead to cancer, the researchers say they still haven't identified the exact mechanism that makes that happen. Still, the study suggests that a newly emerging class of artificially designed molecules (called antagomirs) may be able to block miR 155 expression and be an effective therapeutic strategy in patients with acute lymphoblastic leukemia or high grade lymphomas.


Source:Ohio State University

Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Single stem cells from bone heal a broken heart
3. Successful Test Of Single Molecule Switch Opens The Door To Biomolecular Electronics
4. Single-donor Islet Transplantation Procedure Shows Promise For Patients With Type 1 Diabetes
5. Single gene is genetic switch for fly sexual behavior
6. Single cell amoeba increases MRSA numbers 1000- fold
7. Single molecular mark seen as pivotal for genome compaction in spores and sperm
8. Single molecule extends fat mice lives by reversing gene pathways associated with disease in obese
9. NYU, Rockefeller researchers find complexity of regulation by microRNA genes
10. Molecular steps involved in the creation of gene-silencing microRNAs identified
11. Scientists find microRNAs regulate plant development
Post Your Comments:

(Date:10/29/2015)... Oct. 29, 2015 Today, LifeBEAM ... partnership with 2XU, a global leader in technical ... smart hat with advanced bio-sensing technology. The hat ... to monitor key biometrics to improve overall training ... the two companies will bring together the most advanced ...
(Date:10/26/2015)... PUNE, India , October 26, ... --> --> ... Forecasts 2015 to 2021 as well ... Analysis 2015-2019 research reports to its ... . ...
(Date:10/23/2015)... GOLETA, California , October 23, 2015 ... and SensoMotoric Instruments (SMI) announce a mobile plug and ... captured during interactive real-world tasks SensoMotoric Instruments ... of their established wearable solutions for eye tracking and ... behavior captured with SMI Eye Tracking Glasses 2w ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS; TSX: AEZ) ... remain fundamentally strong and highlights the following developments: ... DSMB recommendation to continue the ZoptEC Phase 3 ... final interim efficacy and safety data , ... with heavily pretreated castration- and Taxane-resistant prostate cancer ...
(Date:11/25/2015)... ... 25, 2015 , ... Jessica Richman and Zachary Apte, founders ... initial angel funding process. Now, they are paying it forward to other microbiome ... investments in the microbiome space. In this, they join other successful entrepreneurs-turned-angels ...
(Date:11/24/2015)... 24, 2015 Halozyme Therapeutics, Inc. (NASDAQ: HALO ) ... New York on Wednesday, December 2 at 9:30 ... president and CEO, will provide a corporate overview. th ... at 1:00 p.m. ET/10:00 a.m. PT . Jim ... provide a corporate overview. --> th Annual Oppenheimer ...
(Date:11/24/2015)... /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS) (TSX: AEZ) (the ... the Toronto Stock Exchange, confirms that as of the ... developments that would cause the recent movements in the ... --> About Aeterna Zentaris Inc. ... Aeterna Zentaris is a specialty biopharmaceutical company engaged in ...
Breaking Biology Technology: