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The let-7 microRNA Family Regulates RAS: Implications for Development and Oncogenesis

es, see Highly Sensitive microRNA Array Performance) was used to assess let-7 expression levels in tissue from 21 different cancer patients, including 12 lung cancer patients with stage IB or IIA squamous cell carcinoma. Interestingly, the lung tumor samples had more than 50% reduction in levels of let-7 miRNA relative to the normal adjacent tissues from the same patients (Figure 3A). Only sporadic reduction in let-7 was detected in breast and colon cancer samples. A similar finding was independently discovered by Takamizawa and colleagues [8]. In addition, several human let-7 family members have been mapped to chromosomal intervals that are deleted in lung cancers [9], providing a possible explanation for the reduced let-7 expression that we observed.


let-7 miRNA, RAS mRNA, and RAS Protein in Lung Cancer

Misexpression or mutation of RAS (HRAS, KRAS, and NRAS) is associated with human cancer [1011]. The observations that (1) RAS is an oncogene, (2) let-7 is down-regulated in lung tumors, and (3) RAS expression is regulated by let-7 miRNA all suggest that reduced let-7 in lung tissue could lead to over-expression of RAS and increased cell proliferation. A prediction from this model is that let-7 miRNA and RAS protein expression should be inversely proportional in lung
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