Proteomics

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Malignant hepatocellular carcinoma cells enrich translation regulatory proteins in exosomes


ABSTRACT: It is known that exosomes (endosome derived vesicles) play important roles in the formation of the tumor microenvironment. Hepatocellular carcinoma (HCC) is a highly malignant cancer, whose malignancy is largely influenced by the tumor microenvironment. The possible role and the specific content of the HCC derived exosomes are however largely unknown. We performed super-SILAC-based mass spectrometry (MS) analyses to interrogate the differential proteins in the exosome of three human HCC cell lines, MHCC97H, MHCCLM3 and Hep3B cells. Exosomal proteins were systematically compared with multi-omics strategies, considering both proteomics and translatomics. With stringent data quality control (quantified unique peptides ≥ 2, FDR ≤ 0.01 at both protein and peptide level), 1907 exosomal proteins were confidently identified from the three HCC cell lines, out of which 469 and 443 exosomal proteins significantly altered in the highly malignant cell lines (MHCC97H/Hep3B and MHCCLM3/Hep3B), respectively. ClueGo and IPA analyses on the differentially expressed proteins (DEPs) revealed that translation and ubiquitination biological processes pathways were significantly more encapsulated in the exosome of higher malignant cell lines. We further observed significantly negative correlation of exosomal protein to cellular protein and translating mRNA in terms of relative abundances comparing the higher malignant cell lines with the low malignant cell line. The negatively correlated genes are also translation regulation-centric. In conclusion, we demonstrated that the exosomal enrichment of translation regulatory proteins is related to the malignant level of HCC cells.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

SUBMITTER: Zhang Jing  

LAB HEAD: Qing-Yu He

PROVIDER: PXD004779 | Pride | 2017-07-18

REPOSITORIES: Pride

Dataset's files

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Action DRS
HEP3B_run1_3.RAW Raw
Hep3B_run1_11.RAW Raw
Hep3B_run1_4.RAW Raw
Hep3B_run1_5.RAW Raw
Hep3B_run1_6.RAW Raw
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Publications

Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

Zhang Jing J   Lu Shaohua S   Zhou Ye Y   Meng Kun K   Chen Zhipeng Z   Cui Yizhi Y   Shi Yunfeng Y   Wang Tong T   He Qing-Yu QY  

Proteomics 20170703 13-14


Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified  ...[more]

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