MicroRNAs link the pathways that control growth during animal development and in disease

June 20, 2012
Credit: Stockphoto.com/arlindo71

Cellular mechanisms that enable healthy growth can spiral out of control and give rise to cancer. For this reason, signal transduction pathways that underlie cell growth are tightly regulated, with multiple checkpoints and extensive cross-talk in between signal cascades that drive cell division and differentiation. Stephen Cohen and co-workers at the A*STAR Institute of Molecular and Cell Biology have identified a new link between growth controlling microRNAs and this cellular circuitry.

MicroRNAs (miRNAs) bind complementary nucleotide sequences on specific target messenger to suppress their expression of proteins. One of these miRNAs, bantam, is known to regulate and survival. Cohen and co-workers set out to determine how this molecule contributes to tissue development in .

Growth control pathways are often complicated. The epidermal growth factor (EGF) signaling pathway is important in growth control and in cancer, EGF receptor (EGFR) sends signals into cells that control many aspects of cellular function, including gene expression. One of the ways EGFR signals is by reducing expression of capicua, a protein that inhibits other growth-promoting genes.

When Cohen and his team experimentally reduced capicua levels, they observed a boost in bantam expression, flagging bantam as a target of capicua-mediated inhibition. More importantly, they learned that bantam in turn feeds back to inhibit expression of capicua. The end result is a that can accelerate the activation or inactivation of EGFR-mediated growth signals — for example, as bantam level rises, capicua level drops, and then bantam level rises even faster to promote cell growth.

The researchers also uncovered an additional layer of complexity in the story. They have previously found that a separate growth regulatory and cancer pathway, triggered by the protein Hippo, also modulates the level of bantam. This places bantam as a link between the Hippo and EGFR pathways; that is, a microRNA could mediate the flow of information between these pathways, so that each can influence the ‘effectiveness’ of the other.

“Regulation of bantam by both EGFR and Hippo reveals an unexpected link between these two growth-regulatory pathways,” explains Cohen. “EGFR activity can change sensitivity to Hippo activity, and vice versa.”

A better understanding of the connections between these pathways could illuminate potential triggers for tumorigenesis, although the connection between fly and human is not a straight line. “The bantam–capicua connection is not conserved in humans,” explains Cohen. “However, we have identified other new growth regulatory targets of bantam and are now studying their roles as tumor suppressors.”

Explore further: New tumor suppressor gene identified

More information: Herranz, H., et al. Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control. Current Biology 22, 1–7 (2012).

Related Stories

New tumor suppressor gene identified

February 13, 2012

A recent study published in Clinical Cancer Research suggests that the protein hVps37A suppresses tumor growth in ovarian cancer. The work, which was funded by the Austrian Science Fund FWF, shows, for the first time, that ...

Recommended for you

Researchers grow retinal nerve cells in the lab

November 30, 2015

Johns Hopkins researchers have developed a method to efficiently turn human stem cells into retinal ganglion cells, the type of nerve cells located within the retina that transmit visual signals from the eye to the brain. ...

Shining light on microbial growth and death inside our guts

November 30, 2015

For the first time, scientists can accurately measure population growth rates of the microbes that live inside mammalian gastrointestinal tracts, according to a new method reported in Nature Communications by a team at the ...

Functional human liver cells grown in the lab

November 26, 2015

In new research appearing in the prestigious journal Nature Biotechnology, an international research team led by The Hebrew University of Jerusalem describes a new technique for growing human hepatocytes in the laboratory. ...


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.