Potential Uses of MicroRNA in Lung Cancer Diagnosis, Prognosis, and Therapy

Qi   Zhao   Wang; William      Xu; Nagy      Habib; Ruian      Xu

Abstract

Lung cancer is the leading cause of death from cancer in the world. Although the molecular network of lung carcinogenesis has been partly known at the levels of genes and proteins, and personalized therapy based on the genetic changes has made considerable progress in the last decade, the high mortality rate is not markedly changed. MicroRNAs (miRNAs), a class of short endogenous RNAs, acting as post-transcriptional regulators of gene expression, are similar with siRNAs in both the biosynthesis and the function steps. While, miRNAs mostly silence gene expression by binding imperfectly matched sequences in the 3 UTR of target mRNA, which is different with siRNAs by targeting ORF of mRNA with a perfectly complementary manner. miRNAs have multiple functions in lung development, and abnormal expression of miRNAs could lead to lung tumorigenesis. The different expression profiles of miRNAs in lung cancer, and the stability of miRNAs in serum, all together make them as new potentially clinical biomarkers for diagnosis and prognosis. Moreover, miRNAs may serve as either novel potential targets acting directly as oncogenes (e.g. miR-17-92 cluster) or directly therapeutic molecules working as tumor suppressor genes (e.g. let-7 family). RNAi technology based on miRNAs has many advantages over siRNAs, such as in vivo stability, highly RNA promoter-compatibility and no overt toxicity. Eventually, it might overcome the present disadvantages and become a good candidate for lung cancer therapy.

Keywords: Lung cancer, microRNA, RNAi, let-7, miR-17-92 cluster, oncogene, tumor suppressor gene

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