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MiR-29 mimic and inhibitor expression in the clear cell renal cell carcinoma cell lines 786-O, A-498 and ACHN

ABSTRACT: The goal of this study was to investigate the regulatory events underlying post-transcriptional changes in gene expression in cancer. We observed that the miR-29 regulon had reccurently increased mRNA stability across multiple cancer types and hypothesized that its down-regulation is responsible at least in part for alterations in the cancer transcriptome. To verify if restoring miR-29 activity can partially reverse these changes, we expressed a miR-29 mimic in the 786-O and A-498 clear cell renal cell carcinoma (ccRCC) lines and performed RNA-sequencing on extracted RNA. We computed differential gene expression in the cell lines expressing the miR-29 mimic, compared to the control sample. We observed that expression of miR-29 mimic partially shifts the transcriptome of cells toward a normal cell state, primarily by down-regulating the majority of genes that are up-regulated in ccRCC tumors, most of which are also miR-29 targets. We observed opposite trends when expressing a miR-29 inhibitor in the ACHN ccRCC cell line. The results suggest that miR-29 downregulation is responsible for changes in the mRNA stability of a considerable number of genes in ccRCC, which can be partially rescued when miR-29 activity is restored.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145088 | GEO | 2022/07/19

REPOSITORIES: GEO

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Project description:MicroRNAs (miRNAs) are an evolutionarily conserved large class of small non-coding RNAs that mediate post-transcriptional silencing of genes and influence a broad spectrum of biological processes ranging from embryonic development to organismal death. Our previous study identified the miR-29 family, three paralogous species of miR-29a/b/c, as the most predominantly expressed small RNA in aged mouse brain compared to the neonate one. Mouse brain miR-29 is highly astrocytic. Its expression is quiescent during early brain development, and then steadily increases to a plateau state around reproductive maturity. To explore the functional relevance of miR-29 expression in early life to the neural physiology of the mouse brain from the mechanistic perspective of mammalian species-specific lifespan, we here undertook a gain-of-function approach through exogenous expression of miR-29 in astrocyte from mouse fetus and surveyed the resulting alteration in both the transcriptional and translational levels. DNA microarray analyses retrieved a total of 5,589 genes showing temporal significant expression changes in the miR-29-transfected fetal astrocytes, and classified them into two gene groups: positively or negatively regulated by miR-29. Mass spectrometry (MS)-based quantification of translational products of miR-29-responsive genes identified 18 species of miR-29 target candidates. We performed functional enrichment analyses utilizing bioinformatics resources to characterize the gene sets thus identified, and found their expression trend that favor the processes for facilitating cell differentiation while supporting normal cell proliferation /survival, which is somewhat different from the functional signatures of miR-29 as observed at adult stages, implying a pleiotropic property of miR-29 depending on the developmental context. Our present results strongly suggest that miR-29 in the developing mouse brain serves as the central coordinator to shift the global gene expression toward adult phenotypes, through which ensure the programmed transition in the life course to the post-developmental/reproductive stage which has inherently been set to delimit the mouse life potential.

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MiR-29 mimic and inhibitor expression in the clear cell renal cell carcinoma cell lines 786-O, A-498 and ACHN

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