PXD036428

PXD036428 is an original dataset announced via ProteomeXchange.

Title	Deregulated Expression of the 14q32 miRNA Cluster in Clear Cell Renal Cell Carcinomas
Description	Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:13.235.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stanley Stevens
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-31 11:18:12	ID requested
1	2023-05-10 13:52:10	announced
⏵ 2	2023-11-14 08:47:15	announced	2023-11-14: Updated project metadata.

Chhabra R, Guergues J, Wohlfahrt J, Rockfield S, Espinoza Gonzalez P, Rego S, Park MA, Berglund AE, Stevens SM, Nanjundan M, Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells. Front Oncol, 13():1048419(2023) [pubmed]

submitter keyword: LPA, DIA,Q-TOF, claudin-1, 14q32, iron, DNMT1, timsTOF Pro, ccRCC, ATXN2

Stanley Stevens, Jr.
contact affiliation	CMMB, University of South Florida
contact email	smstevens@usf.edu
lab head
Stanley Stevens
contact affiliation	University of South Florida
contact email	smstevens@usf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036428
     1. Label: PRIDE project
     2. Name: Deregulated Expression of the 14q32 miRNA Cluster in Clear Cell Renal Cell Carcinomas