Oncogenic Role of <i>miR-483-3p</i> at the <i>IGF2/483</i> Locus

Veronese, Angelo; Lupini, Laura; Consiglio, Jessica; Visone, Rosa; Ferracin, Manuela; Fornari, Francesca; Zanesi, Nicola; Alder, Hansjüerg; D’Elia, Gemma; Gramantieri, Laura; Bolondi, Luigi; Lanza, Giovanni; Querzoli, Patrizia; Angioni, Adriano; Croce, Carlo M.; Negrini, Massimo

doi:10.1158/0008-5472.can-09-4456

Cited by 203 publications

(196 citation statements)

References 33 publications

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“…Human miR-483 is a microRNA located within intron 2 of the IGF2 locus. It has been found that mature miR-483-3p is overexpressed in malignant mesothelioma and Wilms' tumors [34,35]. In addition, the expression level of miR-483-3p is high or extremely high in many common adult human cancers, comprising 30% of cases of colon, breast and liver cancers [35].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

et al. 2010

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a b s t r a c tBoth deregulation of tumor-suppressor genes and misexpression of microRNAs (miRNAs) have been implicated in the development of pancreatic cancer, but their relationship during this process remains less clear. Here, we report that the expression of miR-483-3p is strongly enhanced in pancreatic cancer tissues compared to side normal tissues using a miRNA-array differential analysis. Furthermore, DPC4/Smad4 is identified as a target of miR-483-3p and their expression levels are inversely correlated in human clinical specimens. Ectopic expression of miR-483-3p significantly represses DPC4/Smad4 protein levels in pancreatic cancer cell lines, and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-483-3p as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for the treatment of DPC4/ Smad4-driven pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

et al. 2010

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“…miR-25 and miR-32 could directly target the pro-apoptotic function of Bim, therefore suppressing apoptosis in ovarian and human myeloid leukemia cells, respectively [172,173]. In addition, miR-483-3p might target PUMA, whose enforced expression protects cells from apoptosis [174]. miR-34 decreases the expression of Bcl-2, resulting in an increase in apoptosis [175].…”

Section: Micrornas In Extrinsic and Intrinsic Apoptotic Pathwaysmentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.

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“…70,71 As for the pro-survival BCL-2 family members, BCL-2 and MCL-1 appear to be the prominent targets of miRNA-mediated regulation. Both are targeted by miR-29 and miR-153, [72][73][74] and BCL-2 expression is also regulated by miR-15, miR-16, 75 miR-195 76 and the p53-inducible miR-34.…”

Section: Mcl1mentioning

confidence: 99%

The BCL-2 protein family, BH3-mimetics and cancer therapy

2015

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Escape from apoptosis is a key attribute of tumour cells and facilitates chemo-resistance. The 'BCL-2-regulated' or 'intrinsic' apoptotic pathway integrates stress and survival signalling to govern whether a cancer cell will live or die. Indeed, many pro-apoptotic members of the BCL-2 family have demonstrated tumour-suppression activity in mouse models of cancer and are lost or repressed in certain human cancers. Conversely, overexpression of pro-survival BCL-2 family members promotes tumorigenesis in humans and in mouse models. Many of the drugs currently used in the clinic mediate their therapeutic effects (at least in part) through the activation of the BCL-2-regulated apoptotic pathway. However, initiators of this apoptotic pathway, such as p53, are mutated, lost or silenced in many human cancers rendering them refractory to treatment. To counter such resistance mechanisms, a novel class of therapeutics, 'BH3-mimetics', has been developed. These drugs directly activate apoptosis by binding and inhibiting select antiapoptotic BCL-2 family members and thereby bypass the requirement for upstream initiators, such as p53. In this review, we discuss the role of the BCL-2 protein family in the development and treatment of cancer, with an emphasis on mechanistic studies using well-established mouse models of cancer, before describing the development and already recognised potential of the BH3-mimetic compounds.

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Oncogenic Role of miR-483-3p at the IGF2/483 Locus

Cited by 203 publications

References 33 publications

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

Major apoptotic mechanisms and genes involved in apoptosis

The BCL-2 protein family, BH3-mimetics and cancer therapy

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