There are several groups making headlines that are studying the mir-29 family.
The results clearly demonstrate that higher levels of miR-29c* in MPM predict a more favorable prognosis. Not only was the microRNA able to separate MPM patients by time to progression after surgery, but it also stratified these patients by their survival. Furthermore, the study found that over-expression of miR-29c* in mesothelioma cell lines resulted in significantly decreased proliferation, migration, invasion and colony formation.
- Pass HI, Goparaju C, Ivanov S, Donington J, Carbone M, Hoshen M, Cohen D, Chajut A, Rosenwald S, Dan H, Benjamin S, Aharonov R. (2010) hsa-miR-29c* Is Linked to the Prognosis of Malignant Pleural Mesothelioma. Cancer Res [Epub ahead of print]. [abstract]
UT Southwestern Medical Center – Dr. Eric Olson
- van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN. (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 105(35), 13027-32. [abstract]
The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression.
Ohio State University – Dr. Carlo Croce
The researchers showed that forced expression of MIR29A, MIR29B and MIR29C leads to the re-expression of tumor suppressor genes such as WWOX and FHIT and triggers cell death by apoptosis in lung cancer cell lines, and reduces the size of engrafted tumors by 56 to 94 percent compared with controls. MIR29 is also lost in prostate cancer, and a subset of breast cancers.
- Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA, Andreeff M, Croce CM. (2009) MicroRNA 29b functions in acute myeloid leukemia. Blood 114(26), 5331-41. [abstract]
- Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC. (2008) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14(5), 369-81. [abstract]
- Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T, Liso A, Diverio D, Mancini M, Meloni G, Foa R, Martelli MF, Mecucci C, Croce CM, Falini B. (2008) Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 105(10), 3945-50. [abstract]
- Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM. (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 104(40), 15805-10. [abstract]