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)
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 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.
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."
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).
|Number of mir-21 targets identified|
|This study: 1|
|Cell Res, 2008: 2|
|Canc Res, 2008: 11|