Clarification of a newly-discovered function of Tumor Suppressor Gene

Apr 10, 2012

Synopsis
KAWAI Shinji , Specially Appointed Associate Professor, and AMANO Atsuo , Professor, Graduate School of Dentistry, Osaka University , discovered a new function of a tumor suppressor gene, a world first. Their discovery has given birth to expectations that this will lead to the development of drugs for suppressing the progression and metastasis of cancers. Information regarding their discovery and achievement was published in the April 16th issue of the Journal of Cell Biology .

Background
Breast cancer 1 (BRCA1) is a well-known breast cancer susceptibility gene that plays critical roles in genomic stability and the suppression of breast and ovarian cancer development and progression. Conversely, mutations in BRCA1 predispose one to breast cancer and other cancers. Compounding such a problem, it is known that breast cancer easily metastasizes to bone. BRCA1 also helps control microRNAs (miRNA) and the processing of miRNAs. miRNAs regulate gene expression by suppressing translation and cleavage of target mRNAs. It is first transcribed as a long RNA precursor and then is processed into a short mature RNA having some 20 nucleotides by a processing complex. It is known that abnormal miRNA expressions are found in various cancers.


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This research has clarified that by integrating with the processing complex and directly binding with miRNA precursors, BRCA1 accelerates the  processing of miRNA precursors and controls the amount of mature miRNA. It had been known that BRCA1 suppressed the onset of cancer by repairing chromosome damage; however, this group demonstrated that BRCA1 suppressed the onset of cancer by miRNA processing as well. Furthermore, the group indicated that BRCA1 suppressed not only the onset of cancer, but also various gene expressions.

Future development
This research is part of project "Intractable Oral Disease" promoted by the Graduate School of Dentistry, Osaka University. This research results will greatly contribute to the clarification of the formation of cancers such as bone cancer and oral cancer. It will lead to the development of therapeutic drugs to prevent progression and metastasis of cancer targeting BRCA1 and miRNA.

Technical Glossary