Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10799240 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | 2013 | 9 Pages |
Abstract
In various human malignancies, widespread dysregulation of microRNA (miRNA) expression is reported to occur and affects various cell growth programs. Recent studies suggest that the expression levels of miRNAs that act as tumor suppressors are frequently reduced in cancers because of chromosome deletions, epigenetical changes, aberrant transcription, and disturbances in miRNA processing. MiR-143 and -145 are well-recognized miRNAs that are highly expressed in several tissues, but down-regulated in most types of cancers. However, the mechanism of this down-regulation has not been investigated in detail. Here, we show that DEAD-box RNA helicase 6, DDX6 (p54/RCK), post-transcriptionally down-regulated miR-143/145 expression by prompting the degradation of its host gene product, NCR143/145 RNA. In human gastric cancer cell line MKN45, DDX6 protein was abundantly expressed and accumulated in processing bodies (P-bodies). DDX6 preferentially increased the instability of non-coding RNA, NCR143/145, which encompasses the miR-143/145 cluster, and down-regulated the expression of mature miR-143/145. In human monocytic cell line THP-1, lipopolysaccharide treatment promoted the assembly of P-bodies and down-regulated the expression of NCR143/145 and its miR-143/145 rapidly. In these cells, cycloheximide treatment led to a loss of P-bodies and to an increase in NCR143/145 RNA stability, thus resulting in up-regulation of miR-143/145 expression. These data demonstrate that DDX6 contributed to the control of NCR143/145 RNA stability in P-bodies and post-transcriptionally regulated miR-143/145 expression in cancer cells.
Keywords
NMDCrm1Xrn1AGO17mGLMBDDX6CHXActDpri-miRNAsMicroRNA-143RIPADAPImicroRNA-145IgGDdx5hypoxia inducible factor 1 alpha subunitLPSIPZARGONAUTE 1DDX17PVDFDcp1aGAPDHIFN-β7-methylguanosineHIF1ahnRNPsMiR-145Argonaute 2actinomycin DAgo2immunoglobulin Ginterferon-betabeta-actinprocessing bodiesmiR-143rapid amplification of cDNA endstumor necrosis factor-alphaP-bodiesRISCdiamidino-2-phenylindoleHeterogeneous nuclear ribonucleoproteinsradioimmunoprecipitation assaycycloheximideActbAU-rich elementsTNF-αnonsense-mediated mRNA decayLeptomycin BlipopolysaccharideRaceMicroRNAMiRNAAREPolyvinylidene fluoridepre-miRNAsnegative controlglyceraldehyde-3-phosphate dehydrogenase
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Authors
Akio Iio, Takeshi Takagi, Kohei Miki, Tomoki Naoe, Atsuo Nakayama, Yukihiro Akao,