PXD008584-2

PXD008584 is an original dataset announced via ProteomeXchange.

Title	Synthetic circular RNA functions as a miR-21 sponge to suppress gastric carcinoma cell proliferation
Description	MicroRNA (miRNA) sponges containing miRNA complementary binding sites constitute a potentially useful strategy for miRNA-inhibition therapeutics in cancer patients. Recently, naturally occurring circular RNAs (circRNAs) have been revealed to function as efficient microRNA sponges. We hypothesized that synthetic circRNA sponges targeting oncomiRs could be constructed and used to achieve potentially therapeutic microRNA loss of function. In this study, linear RNA molecules containing five miR-21 binding sites were transcribed in vitro. After dephosphorylation by calf intestinal phosphatase and phosphorylation by T4 polynucleotide kinase, circRNA sponges were circularized using 5’-3’ end ligation by T4 RNA ligase 1. Synthetic circular sponge stability was assayed in the presence of RNase R or fetal bovine serum. Luciferase reporter and cell proliferation assays were performed to assess competitive inhibition of miR-21 activity by circRNA sponges in NCI-N87 gastric cancer cells. Tandem Mass Tag (TMT) labeling proteomics analysis and Western blotting were performed to delineate effects of circRNA sponges on miR-21 downstream targeted proteins. Our experiments revealed that artificial circRNA sponges can be synthesized using enzymatic ligation. These synthetic circRNA sponges are more resistant than their linear RNA counterparts to nuclease degradation in vitro. They effectively suppress the activity of miR-21 on its downstream protein targets, including the important cancer protein DAXX. Finally, they also inhibit gastric cancer cell proliferation. Our results suggest that synthetic circRNA sponges represent a rapid, effective, convenient strategy to achieve loss of miRNA function in vitro, with potential future therapeutic application in vivo.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:13:07.621.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xi Liu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-03 01:24:07	ID requested
1	2018-10-22 06:28:47	announced
⏵ 2	2024-10-22 04:13:08	announced	2024-10-22: Updated project metadata.

Liu X, Abraham JM, Cheng Y, Wang Z, Wang Z, Zhang G, Ashktorab H, Smoot DT, Cole RN, Boronina TN, DeVine LR, Talbot CC, Liu Z, Meltzer SJ, Synthetic Circular RNA Functions as a miR-21 Sponge to Suppress Gastric Carcinoma Cell Proliferation. Mol Ther Nucleic Acids, 13():312-321(2018) [pubmed]

10.1016/j.omtn.2018.09.010;

curator keyword: Biomedical

submitter keyword: Synthetic circular RNA

MicroRNA sponge

MicroRNA loss of function

Gastric carcinoma

Gene therapy

Stephen J. Meltzer
contact affiliation	Division of Gastroenterology, Department of Medicine, and Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
contact email	smeltzer@jhmi.edu
lab head
Xi Liu
contact affiliation	JOHNS HOPKINS UNIVERSITY
contact email	liuxizgq@outlook.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008584
     1. Label: PRIDE project
     2. Name: Synthetic circular RNA functions as a miR-21 sponge to suppress gastric carcinoma cell proliferation