PXD026782

PXD026782 is an original dataset announced via ProteomeXchange.

Title	Serpinc1 acts as a tumor suppressor in hepatocellular carcinoma through inducing apoptosis and blocking macrophage polarization in an ubiquitin-proteasome manner
Description	Serpinc1 is a serine protease inhibitor in the coagulation cascade, but its role in tumor biology remains obscure. Here, we report an unexpected role of serpinc1 in suppression of hepatocellular carcinoma (HCC). In HCC patients, the mRNA and protein expression of serpinc1 is up-regulated, which is negatively correlated with tumor grade, and has a better prognosis than patients with low serpinc1. In addition, patients with high expression of serpinc1 generally have a better tumor immune microenvironment, accompanied by changes in multiple immune cells and mediators. In particular, tumor-promoting M2 macrophages are negatively correlated with serpinc1 expression and the prognosis of HCC patients. In vitro experiments further show that overexpression of serpinc1 inhibits the growth of HCC cells (HepG2 and SMMC7721) by inducing apoptosis. Accordingly, cell co-culture experiments reveal the direct role of serpinc1-overexpressed HCC cells in inhibiting the formation of M2 macrophages. Subsequent unbiased quantitative proteomic and ubiquitinome analysis identify that multiple poly-ubiquitination of proteins involved in signal pathways (such as autophagy, apoptosis, lactate metabolism, and VEGF signaling) are regulated by serpinc1. Overall, these findings establish a serpinc1-dependent ubiquitin-proteasome system to control apoptosis and anti-tumor immunity.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_04:41:02.937.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xu Dacai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-18 03:50:01	ID requested
⏵ 1	2022-02-17 04:41:04	announced

Xu D, Wu J, Dong L, Luo W, Li L, Tang D, Liu J, Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner. Front Oncol, 11():738607(2021) [pubmed]

submitter keyword: serpinc1

apoptosis

liver cancer

macrophage

ubiquitination

Dacai Xu
contact affiliation	Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
contact email	xudacaicn@126.com
lab head
Xu Dacai
contact affiliation	Guangzhou women and children' medical center
contact email	xudacaicn@126.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026782
     1. Label: PRIDE project
     2. Name: Serpinc1 acts as a tumor suppressor in hepatocellular carcinoma through inducing apoptosis and blocking macrophage polarization in an ubiquitin-proteasome manner