PXD021823-1

PXD021823 is an original dataset announced via ProteomeXchange.

Title	Systematic analysis of intronic microRNAs reveals cooperativity within the multi-component FTX locus to promote colon cancer development
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:36:21.275.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dennis Kappei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-05 03:50:59	ID requested
⏵ 1	2024-10-07 13:36:22	announced

Kwok ZH, Zhang B, Chew XH, Chan JJ, Teh V, Yang H, Kappei D, Tay Y, Locus to Promote Colon Cancer Development. Cancer Res, 81(5):1308-1320(2021) [pubmed]

10.1158/0008-5472.can-20-1406;

submitter keyword: microRNAs, A-to-I editing, colon cancer,Long noncoding RNA, post-transcriptional regulation

Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore (CSI), National University of Singapore (NUS)
contact email	dennis.kappei@nus.edu.sg
lab head
Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore
contact email	dennis.kappei@nus.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021823
     1. Label: PRIDE project
     2. Name: Systematic analysis of intronic microRNAs reveals cooperativity within the multi-component FTX locus to promote colon cancer development