PXD024171

PXD024171 is an original dataset announced via ProteomeXchange.

Title	Impaired AGO2/miR-185-3p/NRP1 Axis Promotes Colorectal Cancer Metastasis
Description	Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.
HostingRepository	iProX
AnnounceDate	2021-02-11
AnnouncementXML	Submission_2023-02-19_23:47:42.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xisheng Liu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	TMT6plex reporter fragment
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-15 00:53:53	ID requested
1	2021-02-15 00:54:39	announced
⏵ 2	2023-02-19 23:47:42	announced	2023-02-20: Update publication information.

Liu X, Meng X, Peng X, Yao Q, Zhu F, Ding Z, Sun H, Liu X, Li D, Lu Y, Tang H, Li B, Peng Z, Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis. Cell Death Dis, 12(4):390(2021) [pubmed]

submitter keyword: colorectal cancer, proteomics, AGO2, metastasis

Zhihai Peng
contact affiliation	Hepatobiliary and Pancreatic & Organ Transplantation Surgery Department, Xiang'an Hospital of Xiamen University
contact email	pengzhihai1958@163.com
lab head
Xisheng Liu
contact affiliation	Shanghai General Hospital
contact email	xisheng2019@hotmail.com
dataset submitter

iProX dataset URI