MicroRNA expression and function in cancer. Trends Mol Med

Department of Virology, Immunology and Human Genetics, and Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA.
Trends in Molecular Medicine (Impact Factor: 10.11). 01/2007; 12(12):580-7. DOI: 10.1016/j.molmed.2006.10.006
Source: PubMed

ABSTRACT MicroRNAs are small non-coding RNAs of 19-24 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent work supports a role for miRNAs in the initiation and progression of human malignancies. Large high-throughput studies in patients revealed that miRNA profiling have the potential to classify tumors with high accuracy and predict outcome. Functional studies, some of which involve animal models, indicate that miRNAs act as tumor suppressors and oncogenes. Here, we summarize miRNA-profiling studies in human malignancies and examine the role of miRNAs in the pathogenesis of cancer. We also discuss the implications of these findings for the diagnosis and treatment of cancer.

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    • "c o m / l o c a t e / y b b r c silencing of target genes [11]. The last decade has witnessed the emergence of microRNAs as strategic players in diverse cellular processes, including development, differentiation, proliferation, migration, stress response, angiogenesis, cell death, and carcinogenesis [12] [13] [14] [15] [16] [17]. While miRNAs are linked to a variety of pathological conditions such as neurological disorders, cancer, and metabolic diseases, research studies on the role of miRNAs in wound healing is relatively new and few [18] [19] [20]. "
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    ABSTRACT: Transforming growth factor beta1 (TGFβ1) is a pleiotropic growth factor with a very broad spectrum of effects on wound healing. Chronic non-healing wounds such as diabetic foot ulcers express reduced levels of TGFβ1. On the other hand, our previous studies have shown that the microRNA miR-21 is differentially regulated in diabetic wounds and that it promotes migration of fibroblast cells. Although interplay between TGFβ1 and miR-21 are studied in relation to cancer, their interaction in the context of chronic wounds has not yet been investigated. In this study, we examined if TGFβ1 could stimulate miR-21 in fibroblasts that are subjected to high glucose environment. MiR-21 was, in fact, induced by TGFβ1 in high glucose conditions. The induction by TGFβ1 was dependent on NFκB activation and subsequent ROS generation. TGFβ1 was instrumental in degrading the NFκB inhibitor IκBα and facilitating the nuclear translocation of NFκB p65 subunit. EMSA studies showed enhanced DNA binding activity of NFκB in the presence of TGFβ1. ChIP assay revealed binding of p65 to miR-21 promoter. NFκB activation was also required for the nuclear translocation of Smad 4 protein and subsequent direct interaction of Smad proteins with primary miR-21 as revealed by RNA-IP studies. Our results show that manipulation of TGFβ1–NFκB–miR-21 pathway could serve as an innovative approach towards therapeutics to heal diabetic ulcers.
    Biochemical and Biophysical Research Communications 09/2014; 451(4). DOI:10.1016/j.bbrc.2014.08.035 · 2.28 Impact Factor
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    • "Therefore, the deregulation of their expression may have negative effect on normal cell growth, contributing to the development of diseases such as diabetes, immuno-or neurodegenerative disorders and cancer [11-13]. Many studies have demonstrated that the loss and gain of function of specific miRNAs may be key events in oncogenesis and they can act as either oncogenes (if their genes are amplified or hyper expressed) or tumor-suppressors (in case of deletions or repressions of miRNAs), by acting alone or clustered [14] [15]. Many miRNAs are currently under investigation as diagnostic and prognostic biomarkers, therapeutic targets and as markers of cancer subtypes [16] [17] [18]. "
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    ABSTRACT: The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using Dharmacon(TM) microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value < 0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P < 0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC.
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    • ") mutation with clonal-expansion (MMP) of premalignant cells (Fig. 1) [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Chronic oxidative stress (COS) [12–49] Chronic inflammation/infection and its associated microenvironment c (CIM) [11] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] Defective wound healing (DWH) [52,53,63] [68] [69] [70] [71] [72] Aberrant DNA methylation (ADM) [60,62,67] [73] [74] [75] [76] [77] [78] [79] [80] [81] [82] [83] [84] [85] [86] [87] Aneuploidy and consequent genomic instability d (AGI) [88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99] [100] [101] [102] [103] [104] [105] MicroRNA dysregulation (MRD) [66,83,84,86] [106] [107] [108] [109] [110] [111] [112] [113] [114] [115] [116] [117] [118] [119] [120] [121] [122] [123] [124] [125] [126] [127] [128] [129] [130] [131] a The listed theories are not necessarily mutually exclusive; they each include or imply one or more components that overlap those of other theories listed. b Hypothesized critical oncogene mutations can be somatic or hereditary. "
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