Targeting tumors

Courtesy of Dr. Alexander Nikitin / Cornell University

The paper:

Zhu et al., "MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM 1)," J Biol Chem, 282: 14328-36, 2007. (Cited in 76 papers)

The finding:

A team led by Yin-Yuan Mo, a tumor cell biologist at the Southern Illinois University School of Medicine, measured global protein levels in mouse carcinoma tumors after blocking the activity of the microRNA-21 (mir-21), a cancer-associated small RNA that regulates gene expression. They found that mir-21 fuels tumor growth by silencing tumor suppressor gene 1 (TPM1), a gene that normally makes the muscle protein tropomyosin.

The impact:

The paper makes an "important contribution" to understanding how microRNAs drive cancer by identifying the first target of mir-21, says Kenneth Kosik, a neuroscientist at the University of California, Santa Barbara, who also studies mir-21. The study's high throughput proteomic approach also provides a more reliable way of identifying microRNA targets than by sequence homology, which often produces thousands of erroneous matches, says Mo.

The application:

Rather than trying to target just one signaling pathway implicated in cancer, regulating microRNAs may provide a more global approach to fighting the disease, says Kosik. "One way to try to choke off a pathway is at its neck, and that turns out to be hard," he says. "But microRNA targets potentially represent an opportunity to affect a network in its entirety."

The follow-up:

Last year, both Mo's and Kosik's teams showed that mir-21 targets a host of other cancer-promoting genes (Cell Res, 18:350-9, 2008; Canc Res, 68:8164-72, 2008).