Journal Article•
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Abstract: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
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TL;DR: Investigation of microRNA expression profiles in cisplatin-resistant ovarian ovarian cancer cells found that miR-130a was upregulated in SKOV3/CIS compared to the parentalSKOV3 cells, and PTEN was predicted to be the potential target of miR‑130a.
Abstract: microRNAs (miRNAs) are short non-coding RNA molecules which are involved in the regulation of various biological processes. Drug resistance has become a major obstacle to successful chemotherapy of ovarian cancer. The aim of this study was to investigate microRNA expression profiles in cisplatin-resistant ovarian cancer cells and the role of miR-130a in regulating drug resistance. Analysis of differentially expressed miRNAs between SKOV3 and SKOV3/CIS cells was assessed by miRNA microarrays. Target prediction of miRNAs was determined with the help of PicTar or TargetScan. Among these miRNAs, the expression of miR‑130a was verified using qRT-PCR. The expression of MDR1 mRNA and P-glycoprotein (P-gp) after cellular transfection was examined using qRT-PCR and western blotting, respectively. Cisplatin sensitivity was detected by the MTT assay. We indentified 35 downregulated and 54 upregulated miRNAs in SKOV3/CIS compared to those in SKOV3. We found that miR-130a was upregulated in SKOV3/CIS compared to the parental SKOV3 cells, and PTEN was predicted to be the potential target of miR-130a. Moreover, downregulation of miR-130a could inhibit MDR1 mRNA and P-gp expression and overcome the cisplatin resistance in SKOV3/CIS cells, which indicated that miR-130a may be associated with MDR1/P-gp-mediated drug resistance and plays the role of an intermediate in drug-resistance pathways of PI3K/Akt/PTEN/mTOR and ABC superfamily drug transporters in SKOV3/CIS cells. This study provides important information for the development of targeted gene therapy for reversing cisplatin resistance in ovarian cancer.
119 citations
TL;DR: GO-based fluorescence detection coupled with isothermal gene amplification would be a simple and convenient method for the quantitative detection of miRNA.
Abstract: We have developed a facile fluorometric system for the detection of microRNA (miRNA), using rolling circle amplification (RCA), graphene oxide (GO), and fluorescently labeled peptide nucleic acid (F-PNA). The padlock probe DNA complementary to a target miRNA was selectively ligated to form circular DNA that was then used as the template for RCA. F-PNAs complementary to the target miRNA were annealed to multiple sites of the isothermally amplified single-stranded RCA product (RCAP) containing multiple target miRNA sequences. This F-PNA/RCAP duplex is less adsorbed onto the GO monolayer, thus attenuating the quenching of F-PNA fluorescence by GO. In the absence of target miRNA (and hence the absence of RCA and duplex formation), the free F-PNA is completely adsorbed onto the GO monolayer and fluorescence quenching ensues. Thus, GO-based fluorescence detection coupled with isothermal gene amplification would be a simple and convenient method for the quantitative detection of miRNA.
119 citations
TL;DR: Recent findings on the antiviral activities of cellular miRNAs and the viral counter-responses to the cell's RNAi restriction are summarized.
118 citations
TL;DR: It is reported that miR-34a is a novel target of C/EBPα in granulopoiesis and defined as a novel therapeutic target in AML with CEBPA mutations.
118 citations
TL;DR: The results strongly suggested that miRNA-related SNPs may impact the recurrence and survival in RCC patients and future investigation in larger populations and functional characterizations are necessary to validate these results.
Abstract: We took a polygenic approach to evaluate the effects of 41 potentially functional single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs)-related genes on survival and recurrence among renal cell carcinoma (RCC) patients. During a median follow-up of 21.8 months, among 316 RCC patients, 64 died and 56 developed recurrence. In single-SNP analysis, we identified seven SNPs significantly associated with RCC survival and five SNPs with recurrence. The most significant associations were SNPs in GEMIN4 with the variant alleles of both rs7813 and rs910925 associated with 1.74-fold [95% confidence interval (CI) = 1.15-2.62] increased risk of death, whereas the variant allele of rs3744741 conferred a decreased risk of death [hazard ratio (HR) = 0.39; 95% CI = 0.19-0.77]. Several SNPs belonging to the pre-miRNA and were identified to be significantly associated with RCC recurrence. Haplotypes of DICER and DROSHA were also associated with altered patient survival and recurrence. More importantly, we observed cumulative effects of multiple SNPs on RCC survival. Compared with subjects carrying zero to two unfavorable genotypes, those carrying three to five and six and more unfavorable genotypes had an increased risk of death with a HR of 2.49 (95% CI = 1.24-5.00) and 6.66 (95% CI = 2.49-17.86), respectively, with significant dose-response trend (P for trend<0.001). As the first study of miRNA-related genetic polymorphisms on RCC clinical outcome, our results strongly suggested that miRNA-related SNPs may impact the recurrence and survival in RCC patients. Future investigation in larger populations and functional characterizations are necessary to validate these results.
118 citations
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
TL;DR: Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin- 4 regulates lin- 14 translation via an antisense RNA-RNA interaction.
11,932 citations
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Abstract: Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.
9,470 citations
TL;DR: The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
5,246 citations
TL;DR: The two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.
Abstract: Hundreds of small RNAs of approximately 22 nucleotides, collectively named microRNAs (miRNAs), have been discovered recently in animals and plants. Although their functions are being unravelled, their mechanism of biogenesis remains poorly understood. miRNAs are transcribed as long primary transcripts (pri-miRNAs) whose maturation occurs through sequential processing events: the nuclear processing of the pri-miRNAs into stem-loop precursors of approximately 70 nucleotides (pre-miRNAs), and the cytoplasmic processing of pre-miRNAs into mature miRNAs. Dicer, a member of the RNase III superfamily of bidentate nucleases, mediates the latter step, whereas the processing enzyme for the former step is unknown. Here we identify another RNase III, human Drosha, as the core nuclease that executes the initiation step of miRNA processing in the nucleus. Immunopurified Drosha cleaved pri-miRNA to release pre-miRNA in vitro. Furthermore, RNA interference of Drosha resulted in the strong accumulation of pri-miRNA and the reduction of pre-miRNA and mature miRNA in vivo. Thus, the two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.
5,191 citations