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MiR-133b targets antiapoptotic genes and enhances death receptor-induced apoptosis

ABSTRACT: Despite the importance of microRNAs (miRs) for regulation of the delicate balance between cell proliferation and death, only scarce evidence is currently available on their specific involvement during death receptor (DR)-mediated apoptosis. Transfection of mature miR-133b into resistant HeLa cells rendered these sensitive to tumor necrosis factor-alpha (TNFα)-induced cell death. Similarly, miR-133b treatment resulted in exacerbated proapoptotic responses to TNF-related apoptosis-inducing ligand (TRAIL) or an activating antibody to CD95 (Fas/APO1). Comprehensive analysis, encompassing global RNA and protein expression profiling performed by microarray experiments and pulsed stable isotope labeling by amino acids in cell culture (pSILAC), led to the discovery of the antiapoptotic proteins Fas apoptosis inhibitory molecule (FAIM) and glutathione-S-transferase pi (GSTP-1) as immediate miR-133b targets. In-vivo, expression of miR-133b in tumor specimens of prostate cancer patients could be proven as significantly downregulated in 75% of the cases, when compared with matched healthy tissue. Furthermore, introduction of synthetic miR-133b into an ex-vivo model of prostate cancer resulted in impaired proliferation and cellular metabolic activity. These results reveal the ability of a single miR to influence major apoptosis pathways, suggesting an essential role for this molecule during the process of cellular transformation, tumor generation and tissue homeostasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24613 | GEO | 2015/01/01

SECONDARY ACCESSION(S): PRJNA132433

REPOSITORIES: GEO

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