microRNAs as oncogenes and tumor suppressors

Abstract

microRNAs (miRNAs) are a new class of non-protein-coding, endogenous, small RNAs. They are important regulatory molecules in animals and plants. miRNA regulates gene expression by translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-guided rapid deadenylation. Recent studies show that some miRNAs regulate cell proliferation and apoptosis processes that are important in cancer formation. By using multiple molecular techniques, which include Northern blot analysis, real-time PCR, miRNA microarray, up- or down-expression of specific miRNAs, it was found that several miRNAs were directly involved in human cancers, including lung, breast, brain, liver, colon cancer, and leukemia. In addition, some miRNAs may function as oncogenes or tumor suppressors. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites, suggesting that miRNAs may play a more important role in the pathogenesis of a limited range of human cancers than previously thought. Overexpressed miRNAs in cancers, such as mir-17-92, may function as oncogenes and promote cancer development by negatively regulating tumor suppressor genes and/or genes that control cell differentiation or apoptosis. Underexpressed miRNAs in cancers, such as let-7, function as tumor suppressor genes and may inhibit cancers by regulating oncogenes and/or genes that control cell differentiation or apoptosis. miRNA expression profiles may become useful biomarkers for cancer diagnostics. In addition, miRNA therapy could be a powerful tool for cancer prevention and therapeutics.

Impaired Biomechanical Properties of Diabetic Skin

“…For instance, the half-life of casein mRNA is lengthened when prolactin is present, thus improving milk production. 36 Alternatively, studies have demonstrated that lack of microRNA production can permit uncontrolled cellular proliferation in the setting of leukemia 37 and breast cancer. 38 Recently, Roggli et al 39 demonstrated in a mouse diabetic model that inflammatory cytokines elicit production of microRNA species that may be involved in the development of pancreatic ␤-cell failure, whereas the direct connection between increased production of microRNA targeting collagen gene expression and diabetes is still unclear.…”

Upregulation of miR-21 by Ras in vivo and its role in tumor growth

“…The involvement of microRNAs (miRNAs) in cancer emerged from several reports showing that they are aberrantly expressed in neoplastic tissues (Lu et al, 2005;Volinia et al, 2006) The identification of several targets of miRNAs involved in cancer has led to the widely accepted idea that networks comprising classical oncogenes or tumor suppressors and miRNAs have pivotal roles in cancer initiation, progression and metastatization (Esquela-Kerscher and Slack, 2006;Zhang et al, 2007). Deregulation of miRNAs expression in cancer can occur by genetic mechanisms including amplification, deletion and mutation, as well as by epigenetic silencing (Calin et al, 2004;Zhang et al, 2006).…”

miRNA expression profiling of lung adenocarcinomas: correlation with mutational status

“…They are expressed in a tissue-specific manner, and has been shown that the pattern of expression accurately define the specific cancer types. [8][9][10][11][12][13][14] Prognostic and diagnostic significance of miRNA expression has been reported in several malignancies, including chronic lymphocytic leukemia, breast, pancreas, colon and lung carcinomas. [15][16][17][18][19] Let-7 was the first miRNA reported to be aberrantly expressed in lung carcinomas.…”