MicroRNA expression and function in cancer.
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.
SourceAvailable from: Zhanjun Guo[Show abstract] [Hide abstract]
ABSTRACT: Recent studies demonstrate that microRNA-related single-nucleotide polymorphisms (miR-SNPs) are associated with the development of numerous human cancers. In this study, we investigated six miR-SNPs in microRNA processing machinery genes, including rs11077 of the XPO5 gene, rs14035 of the RAN gene, rs3742330 of the Dicer gene, rs9623117 of the TNRC6B gene, rs197412 of the GEMIN3 gene, and rs2740348 of the GEMIN4 gene, in gastric cancer patients and subsequently evaluated their potential roles in gastric cancer risk in a case control study. The results indicate that the C/C genotype of rs14035 from RAN, the A/A genotype of rs3742330 from Dicer, and the T/T genotype of rs9623117 from TNRC6B are significantly associated with gastric cancer risk. In conclusion, these miR-SNPs can be used as predictive biomarkers in gastric cancer.OncoTargets and Therapy 01/2015; 8:567-71. DOI:10.2147/OTT.S79150 · 1.34 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs which regulate key cellular processes through a negative post-transcriptional regulation of their target mRNAs. They can act either as oncogenes or as tumor suppressors or as both, depending on the specific tissue expression. Oncogenic miRNAs act directly on mRNAs from genes with pro-apoptotic or anti-proliferative roles. Conversely, tumor-suppressor miRNAs repress the expression of genes with oncogenic functions. Deregulation of many of these miRNAs has been associated with tumorigenesis in various cancers and recent studies have shown evidences of abnormal miRNA expression in gallbladder cancer. Here, we review our current understanding of the expression changes in tumor-suppressor miRNAs (miR-1, miR-145, miR-135a-5p, miR-26a, miR-34a, miR-335, miR-130a and miR-218-5p) and oncogenic miRNAs (miR-155, miR-20a and miR-182) and its implication in the pathogenesis of gallbladder cancer and their potential as diagnostic and prognostic markers.
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ABSTRACT: Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase family whose members have been implicated in tumor suppression in many cancer models. In many cancers, loss of PP2A activity has been associated with tumorigenesis and drug resistance. Loss of PP2A results in failure to turn off survival signaling cascades that drive drug resistance such as those regulated by protein kinase B. PP2A is responsible for modulating function and controlling expression of tumor suppressors such as p53 and oncogenes such as BCL2 and MYC. Thus, PP2A has diverse functions regulating cell survival. The importance of microRNAs (miRs) is emerging in cancer biology. A role for miR regulation of PP2A is not well understood; however, recent studies suggest a number of clinically significant miRs such as miR-155 and miR-19 may include PP2A targets. We have recently found that a PP2A B subunit (B55α) can regulate a number of miRs in acute myeloid leukemia cells. The identification of a miR/PP2A axis represents a novel regulatory pathway in cellular homeostasis. The ability of miRs to suppress specific PP2A targets and for PP2A to control such miRs can add an extra level of control in signaling that could be used as a rheostat for many signaling cascades that maintain cellular homeostasis. As such, loss of PP2A or expression of miRs relevant for PP2A function could promote tumorigenesis or at least result in drug resistance. In this review, we will cover the current state of miR regulation of PP2A with a focus on leukemia. We will also briefly discuss what is known of PP2A regulation of miR expression.Frontiers in Oncology 02/2015; 5:43. DOI:10.3389/fonc.2015.00043