Proteomics

Dataset Information

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Systematic analysis of intronic microRNAs reveals cooperativity within the multi-component FTX locus to promote colon cancer development


ABSTRACT: Approximately half of all microRNAs reside within intronic regions and are often co-transcribed with their host genes. However, most studies on intronic microRNAs focus on individual microRNAs, and conversely most studies on protein-coding and non-coding genes frequently ignore any intron-derived microRNAs. We hypothesize that the individual components of such multi-genic loci may play cooperative or competing roles in driving disease progression, and that examining the combinatorial effect of these components would uncover deeper insights into their functional importance. To address this, we perform systematic analyses of intronic microRNA:host loci in colon cancer. We observe that the FTX locus, comprising of a long non-coding RNA FTX and multiple intronic microRNAs, is highly upregulated in cancer and demonstrate that cooperativity within this multi-component locus promotes cancer growth. In addition, we show that FTX interacts with DHX9 and DICER and delineate its novel roles in regulating A-to-I RNA editing and microRNA expression. These results show for the first time that a long non-coding RNA can regulate A-to-I RNA editing, further expanding the functional repertoire of long non-coding RNAs. We further demonstrate the inhibitory effects of intronic miR-374b and -545 on the tumor suppressors PTEN and RIG-I to enhance the proto-oncogenic PI3K-AKT signaling. Finally, we show that intronic miR-421 may exert an autoregulatory effect on miR-374b and -545. Taken together, our data unveil the intricate interplay between intronic microRNAs and their host transcripts in the modulation of key signaling pathways and disease progression, adding new perspectives to the functional landscape of multi-genic loci.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Dennis Kappei  

LAB HEAD: Dennis Kappei

PROVIDER: PXD021823 | Pride | 2021-01-05

REPOSITORIES: Pride

Dataset's files

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20180912_QPC_CC_CSI_YT_ZH_HCT116_FTX_RNA.zip Other
20180912_QPC_CC_CSI_YT_ZH_HCT116_FTX_RNA_for.raw Raw
20180912_QPC_CC_CSI_YT_ZH_HCT116_FTX_RNA_rev.raw Raw
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Publications

Systematic Analysis of Intronic miRNAs Reveals Cooperativity within the Multicomponent <i>FTX</i> Locus to Promote Colon Cancer Development.

Kwok Zhi Hao ZH   Zhang Bin B   Chew Xiao Hong XH   Chan Jia Jia JJ   Teh Velda V   Yang Henry H   Kappei Dennis D   Tay Yvonne Y  

Cancer research 20201110 5


Approximately half of all miRNA reside within intronic regions and are often cotranscribed with their host genes. However, most studies of intronic miRNA focus on individual miRNA, while conversely most studies of protein-coding and noncoding genes frequently ignore any intron-derived miRNA. We hypothesize that the individual components of such multigenic loci may play cooperative or competing roles in driving disease progression and that examining the combinatorial effect of these components wo  ...[more]

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