Dataset Information

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway.

ABSTRACT: Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation. Reinforced expression of miR-300 significantly suppressed the migration of BCa cells. We carried out a search of online databases to predict potential targets of miR-300. Further studies determined that miR-300 directly targeted SP1 and suppressed its expression by specifically binding to its 3'-untranslated region. Meanwhile, downregulated MMP9 may be the final effector of BCa cell mobility. Small interference RNAs silencing SP1 phenocopied the effects of miR-300 overexpression, while restoration of SP1 expression partially rescued the inhibition of metastasis induced by miR-300 overexpression in BCa cells. In conclusion, we unveiled a miR-300/SP1/MMP9 pathway in BCa. These findings demonstrate that miR-300 is a promising tumor suppressor in BCa.

SUBMITTER: Yan H

PROVIDER: S-EPMC6343712 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway.

Yan Huaqing H Li Jiangfeng J Ying Yufan Y Xie Haiyun H Chen Hong H Xu Xin X Zheng Xiangyi X

Cell cycle (Georgetown, Tex.) 20181218 24

Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation. Reinforced expression of miR-300 significantly suppressed the migration of BCa ...[more]

PMID: 30526300

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Project description:BackgroundGenomic imprinting is an exception to Mendelian genetics in that imprinted genes are expressed monoallelically, dependent on parental origin. In mammals, imprinted genes are critical in numerous developmental and physiological processes. Aberrant imprinted gene expression is implicated in several diseases including Prader-Willi/Angelman syndromes and cancer.Methodology/principal findingsTo identify novel imprinted genes, transcription profiling was performed on two uniparentally derived cell lines, androgenetic and parthenogenetic primary mouse embryonic fibroblasts. A maternally expressed transcript termed Imprinted RNA near Meg3/Gtl2 (Irm) was identified and its expression studied by Northern blotting and whole mounts in situ hybridization. The imprinted region that contains Irm has a parent of origin effect in three mammalian species, including the sheep callipyge locus. In mice and humans, both maternal and paternal uniparental disomies (UPD) cause embryonic growth and musculoskeletal abnormalities, indicating that both alleles likely express essential genes. To catalog all imprinted genes in this chromosomal region, twenty-five mouse mRNAs in a 1.96Mb span were investigated for allele specific expression.Conclusions/significanceTen imprinted genes were elucidated. The imprinting of three paternally expressed protein coding genes (Dlk1, Peg11, and Dio3) was confirmed. Seven noncoding RNAs (Meg3/Gtl2, Anti-Peg11, Meg8, Irm/"Rian", AK050713, AK053394, and Meg9/Mirg) are characterized by exclusive maternal expression. Intriguingly, the majority of these noncoding RNA genes contain microRNAs and/or snoRNAs within their introns, as do their human orthologs. Of the 52 identified microRNAs that map to this region, six are predicted to regulate negatively Dlk1, suggesting an additional mechanism for interactions between allelic gene products. Since several previous studies relied heavily on in silico analysis and RT-PCR, our findings from Northerns and cDNA cloning clarify the genomic organization of this region. Our results expand the number of maternally expressed noncoding RNAs whose loss may be responsible for the phenotypes associated with mouse pUPD12 and human pUPD14 syndromes.

Dataset Information

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway.

Publications

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway.

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