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At least 721 records · Page 40Linked to original sources
PubMed2006

MicroRNAs as a potential magic bullet in cancer.

Genes that control cell differentiation and development are frequently mutated in human cancer. Micro (mi)RNAs are small regulatory RNAs that are emerging as important regulators of cell division/differentiation and human cancer genes. In this review, the miRNA cancer connection is discussed and the possibility of using this novel, but potentially powerful new therapy, involving miRNAs, to treat cancers is speculated on. For example, lung cancer is the major cause of cancer deaths in the USA, but existing therapies fail to treat this disease in the overwhelming majority of cases. The let-7 miRNA is one of a number of 'oncomirs', natural miRNA tumor suppressors in lung tissue, which may prove useful in treating lung cancer or enhancing current treatments for lung cancer.

Animals↗
PubMed2006

GW bodies, microRNAs and the cell cycle.

GW bodies (GWBs) are cytoplasmic foci initially identified through the use of an autoimmune serum targeting the marker protein, GW182. GWBs were first considered as both storage centers for a specific subset of mRNAs and degradation sites for mRNAs. Interestingly, they are known to vary in size and number throughout the cell cycle and are largest in size and most abundant in number during the late S and G2 phases. Recent studies have linked RNA interference to GWBs, in that disruption or disassembly of GWBs was demonstrated to impair siRNA and miRNA silencing activity. As miRNAs are implicated in the regulation of cell cycle progression and cell proliferation, it is very likely that GWBs, the critical intracellular structures for miRNA function, may very well be also linked to this cellular process.

Autoantigens↗
PubMed2006

microRNA-mediated silencing inside P-bodies.

Cytoplasmic processing bodies, or P-bodies, contain a high concentration of enzymes and factors required for mRNA turnover and translational repression. Recent studies provide evidence that the mRNAs silenced by miRNAs are localized to P-bodies for storage or degradation, perhaps in adjacent subcompartments. mRNP remodeling, potentially induced by miRISC or RNA helicase activity, may cause the modification of the translation initiation complex at the 5' end of mRNA, following translational repression and localization to P-bodies. Further remodeling in P-bodies may facilitate access of the decapping complex to the cap structure, thus inducing mRNA degradation. However, with appropriate signals, stored mRNAs in P-bodies could be released and returned to the translational machinery through mechanisms requiring binding of regulatory proteins to the 3' UTR of mRNAs. Here a model is proposed to explain the repression and degradation stages of the mRNAs within PBs. This model includes preservation or disruption of a stable closed loop structure of the mRNAs, compartmentalization in PBs and mRNA escape triggered by additional binding proteins.

Cell Compartmentation↗
PubMed2004

Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation.

The study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA (siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down (evident after 6 hr) precedes any decrease in targeted message (evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.

Animals↗
PubMed2006

miRNAs regulate miRNAs: coordinated transcriptional and post-transcriptional regulation.

microRNAs are short single-stranded RNA molecules that negatively regulate gene expression at post-transcriptional level. Recently it has been demonstrated that microRNAs are involved in many physiological processes, including differentiation and development. Moreover, this class of tiny regulators is drammatically involved in many pathological processes, like tumors and genetic diseases. A main issue is how microRNA processing and expression are regulated: thanks to recent findings, we are beginning to get insight into this critical aspect of microRNA biology, but we are far from understanding these processes in all their complexity. In particular, microRNA coordinated expression with other regulatory molecules, such as transcription factors, is still under investigation. We depleted microRNA 221 and 222 and found that the microRNA signature of Human Umbilical Vein Endothelial Cells was affected as a consequence: 9 microRNAs were up-regulated and 23 microRNAs were down-regulated. We propose a model in which a complex network involving coexpressed microRNAs and transcription factors is affected by single microRNA-variations, with the result that microRNA expression profile is in turn modified.

Cell Differentiation↗
PubMed2005

Small RNAs in human brain development and disorders.

Small RNA is a variable and abundant type of non-coding RNAs in brain. The function of these RNAs is mainly unknown. A specific class of small RNA, microRNA, is dynamically regulated in neurogenesis and in embryo brain development. The genes for synaptic formation and some mental retardation disorders are putative targets for microRNA predicted by computational algorithms. The molecular pathways for mental development, common forms of autisms, schizophrenia, and affective disorders have yet to be elucidated. The hypothesis proposed here is that small regulatory RNAs, specifically microRNAs, play a role in human brain development and pathogenesis of brain disorders, especially of neurodevelopmental conditions. Pilot tests using comprehensive arrays of microRNAs demonstrate that microRNAs derived from postmortem human brains are applicable for microRNA expression profiling. The abundant expression of many regulatory small RNAs in human brain implies their biological role that must be tested by functional assays in neurons and by genetic and comparative expression profiling.

Brain↗
PubMed2024

ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma.

BACKGROUND: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. METHODS: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. RESULTS: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. CONCLUSIONS: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Humans↗