Genomic DNA copy-number alterations of the let-7 family in human cancers.

Genomic DNA copy-number alterations of the let-7 family in human cancers.

Blog Article

In human cancer, expression of the let-7 family is significantly reduced, and this is associated with shorter survival times in patients.However, the mechanisms leading to let-7 downregulation in cancer are still largely unclear.Since an alteration in copy-number is one of the causes of gene deregulation CALENDULA in cancer, we examined copy number alterations of the let-7 family in 2,969 cancer specimens from a high-resolution SNP array dataset.

We found that there was a reduction in the copy number of let-7 genes in a cancer-type specific manner.Importantly, focal deletion of four let-7 family members was found in three cancer types: medulloblastoma (let-7a-2 and let-7e), breast cancer (let-7a-2), and ovarian cancer (let-7a-3/let-7b).For example, the genomic locus harboring let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients.

We also found a positive correlation between the copy number of let-7b and mature let-7b expression in ovarian cancer.Finally, we showed that restoration of let-7b expression dramatically reduced ovarian tumor growth in vitro and in vivo.Our results indicate that copy number deletion is an important mechanism leading to the downregulation of expression of specific let-7 family members in medulloblastoma, breast, and ovarian cancers.

Restoration of let-7 expression in tumor cells could provide DIURETIC FORMULA a novel therapeutic strategy for the treatment of cancer.