A 3′-Untranslated Region (3′UTR) Induces Organ Adhesion by Regulating miR-199a* Functions

Lee, Daniel Y.; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W.; Deng, Zhaoqun; Yang, Burton B.

doi:10.1371/journal.pone.0004527

Cited by 97 publications

(111 citation statements)

References 67 publications

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“…Our systematic studies in vertebrates parallel the results from our Drosophila studies (Okamura et al 2008) and greatly extend recent reports indicating functional targets of specific mammalian miRNA* species, such as miR-9a* (Packer et al 2008;Yoo et al 2009), miR-199* (Kim et al 2008Lee et al 2009;Lin et al 2009), miR-30a* (Ro et al 2007), and miR-18a* (Tsang and Kwok 2009). Altogether, these data indicate that the regulatory impact of miRNA* species on mammalian genomes is much more substantial than is currently envisaged.…”

Section: Mirna* Species Can Repress Targets Via Perfect Sites and Seesupporting

confidence: 86%

Widespread regulatory activity of vertebrate microRNA* species

Yang

Phillips

Betel

et al. 2010

RNA

312

240

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An obligate intermediate during microRNA (miRNA) biogenesis is an~22-nucleotide RNA duplex, from which the mature miRNA is preferentially incorporated into a silencing complex. Its partner miRNA* species is generally regarded as a passenger RNA, whose regulatory capacity has not been systematically examined in vertebrates. Our bioinformatic analyses demonstrate that a substantial fraction of miRNA* species are stringently conserved over vertebrate evolution, collectively exhibit greatest conservation in their seed regions, and define complementary motifs whose conservation across vertebrate 39-UTR evolution is statistically significant. Functional tests of 22 miRNA expression constructs revealed that a majority could repress both miRNA and miRNA* perfect match reporters, and the ratio of miRNA:miRNA* sensor repression was correlated with the endogenous ratio of miRNA:miRNA* reads. Analysis of microarray data provided transcriptome-wide evidence for the regulation of seedmatched targets for both mature and star strand species of several miRNAs relevant to oncogenesis, including mir-17, mir-34a, and mir-19. Finally, 39-UTR sensor assays and mutagenesis tests confirmed direct repression of five miR-19* targets via star seed sites. Overall, our data demonstrate that miRNA* species have demonstrable impact on vertebrate regulatory networks and should be taken into account in studies of miRNA functions and their contribution to disease states.

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Section: Mirna* Species Can Repress Targets Via Perfect Sites and Seesupporting

confidence: 86%

Widespread regulatory activity of vertebrate microRNA* species

Yang

Phillips

Betel

et al. 2010

RNA

312

240

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“…The cell numbers were counted by using trypan blue staining as described (Wang et al, 2008a;Lee et al, 2009). The experiments were repeated three times.…”

Section: Mir-93 In Angiogenesis L Fang Et Almentioning

confidence: 99%

MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8

et al. 2010

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It has been reported that the miR-106bB25 cluster, a paralog of the miR-17B92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106bB25 cluster is not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106bB25 cluster, in angiogenesis and tumor formation. We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation. In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrinb8 is a target of miR-93. Higher levels of integrin-b8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-b8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-b8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-b8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.

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“…More recently studies have proposed that miRNAs may stabilise their target mRNAs as well [27,[30][31][32][33][34][35][36]. This study further investigated the possibility of the stabilisation effect of mRNAs on their target mRNAs by analysing whether individual samples with higher miRNA expression levels might tend to have higher or consistent expression levels of their target mRNAs.…”

Section: Discussionmentioning

confidence: 94%

“…More recently studies suggested that these non-coding RNAs may stabilise the expression of their target messenger RNAs (mRNAs) [27,[30][31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts

Tulay

Naja

Cascales-Roman

et al. 2015

J Assist Reprod Genet

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Purpose The aim of the study is to investigate the regulation of DNA repair genes by microRNAs (miRNAs). miRNAs are short non-coding RNAs that regulate transcriptional and post-transcriptional gene silencing. Several miRNAs that are expressed during preimplantation embryo development have been shown or are predicted to target genes that regulate cell cycle checkpoints and DNA repair in response to DNA damage. Methods This study compares the expression level of 20 miRNAs and 9 target transcripts involved in DNA repair. The statistical significance of differential miRNA expression between oocytes and blastocysts was determined by t test analysis using the GraphPad Prism v6 software. The possible regulatory roles of miRNAs on their target messenger RNAs (mRNAs) were analysed using a Pearson correlation test. Results This study shows for the first time that several miRNAs are expressed in human oocytes and blastocysts that target key genes involved in DNA repair and cell cycle checkpoints. Blastocysts exhibited statistically significant lower expression levels for the majority of miRNAs compared to oocytes (p<0.05). Correlation analyses showed that there was both inverse and direct association between miRNAs and their target mRNAs. Conclusions miRNAs target many mRNAs including ones involved in DNA repair mechanisms. This study suggests that miRNAs and their target mRNAs involved in DNA repair are expressed in preimplantation embryos. Similar to the miRNAs expressed in adult tissues, these miRNAs seem to have regulatory roles on their target DNA repair mRNAs during preimplantation embryo development.

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A 3′-Untranslated Region (3′UTR) Induces Organ Adhesion by Regulating miR-199a* Functions

Cited by 97 publications

References 67 publications

Widespread regulatory activity of vertebrate microRNA* species

Widespread regulatory activity of vertebrate microRNA* species

MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8

Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts

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