PXD051359

PXD051359 is an original dataset announced via ProteomeXchange.

Title	Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome
Description	The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T-cell recruitment. CircDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging IGF2BP3 half-life, which in turn sustains the mRNA level of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators. Production of CXCL10 and IL-9 by CRC cells is elicited through JAK-STAT1 signaling, in turn promoting the chemotactic and cytolytic activities of CD8+ T cells. Clinical evidence associates increased circDNA2v expression in CRC tissues with reduction in CD8+ T-cell infiltration and worse outcomes. The regulatory relationship between circDNA2v, cellular senescence and tumor infiltrating lymphocytes thus provides a rationale approach for improving immunotherapy in CRC.
HostingRepository	iProX
AnnounceDate	2024-04-11
AnnouncementXML	Submission_2024-12-08_20:16:47.691.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuang Wu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-11 01:41:58	ID requested
1	2024-04-11 01:42:27	announced
⏵ 2	2024-12-08 20:16:48	announced	2024-12-09: Update information.

Wu S, Dai X, Xia Y, Zhao Q, Zhao H, Shi Z, Yin X, Liu X, Zhang A, Yao Z, Zhang H, Li Q, Thorne RF, Zhang S, Sheng W, Hu W, Gu H, Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome. Cell Rep, 43(4):114111(2024) [pubmed]

submitter keyword: circular RNA, circDNA2v, IGF2BP3, c-Myc, senescence, CXCL10, IL-9, CD8+T cells

Hao Gu
contact affiliation	Anhui Medical University
contact email	guhao@ahmu.edu.cn
lab head
Shuang Wu
contact affiliation	Anhui Medical University
contact email	wushuang1994326@126.com
dataset submitter

iProX dataset URI