PXD054740-1

PXD054740 is an original dataset announced via ProteomeXchange.

Title	RPL6 interacts with HMGCS1 to stabilize HIF-1α by activating cholesterol biosynthesis in hepatocellular carcinoma.
Description	The identification of predictive markers to determine the premetastatic phase before metastasis is critical for developing effective strategies for early detection and prevention. By applying the dynamic network biomarker (DNB) approach to analyze time-series transcriptomic data from a pulmonary metastasis HCC mouse model, we revealed that the premetastatic phase occurred during the fourth week after implantation. A total of 142 DNB genes were identified as functionally important biomarkers of this critical phase, among which 60S ribosomal protein L6 (RPL6) was a core DNB member. RPL6 was significantly upregulated in HCC tissues with extrahepatic metastasis and was strongly correlated with poor prognosis in HCC patients. RPL6 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, RPL6 directly bound to the HMGCS1 mRNA 3’UTR, a rate-limiting enzyme in cholesterol biosynthesis, thus increasing HMGCS1 mRNA stability and protein expression and subsequently elevating intracellular cholesterol level. Elevated cholesterol inhibited of the ubiquitin-dependent degradation of HIF-1α by binding to PHD2 and reducing PHD2-mediated hydroxylation of HIF-1α, which further resulted in HIF-1α signaling pathway activation. Moreover, RPL6, HMGCS1 and HIF-1α were coexpressed in HCC tissues with extrahepatic metastasis. Taken together, this study provides new insights into the dynamic transcriptome profiles of HCC pulmonary metastasis and establishes an important role for the RPL6-HMGCS1-HIF-1α axis in HCC metastasis, suggesting potential prognostic biomarkers and therapeutic targets in HCC.
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-19_16:07:09.862.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Minli Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-08 22:09:21	ID requested
⏵ 1	2025-10-19 16:07:10	announced

10.1002/advs.202501373;

Yang M, Cheng S, Gu H, Zhong S, Zhang D, He X, Chen W, Deng H, Ren J, Chen P, Tan M, Zhang H, Li F, Zhang Z, Hu Y, Chen J, by Promoting Cholesterol Production in Hepatocellular Carcinoma. Adv Sci (Weinh), 12(38):e01373(2025) [pubmed]

submitter keyword: Hepatocellular carcinoma

Metastasis

RPL6

HMGCS1

Cholesterol

Minli Yang
contact affiliation	Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
contact email	604092845@qq.com
lab head
Minli Yang
contact affiliation	Chongqing medical university
contact email	604092845@qq.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD054740

PRIDE project URI

• PRIDE
  1. PXD054740
     1. Label: PRIDE project
     2. Name: RPL6 interacts with HMGCS1 to stabilize HIF-1α by activating cholesterol biosynthesis in hepatocellular carcinoma.