Dataset Information

Deregulated Expression of the 14q32 miRNA Cluster in Clear Cell Renal Cell Carcinomas

ABSTRACT: 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.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Renal Tubule

DISEASE(S): Papillary Renal Cell Carcinoma

SUBMITTER: Stanley Stevens

LAB HEAD: Stanley Stevens, Jr.

PROVIDER: PXD036428 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells.

Chhabra Ravneet R Guergues Jennifer J Wohlfahrt Jessica J Rockfield Stephanie S Espinoza Gonzalez Pamela P Rego Shanon S Park Margaret A MA Berglund Anders E AE Stevens Stanley M SM Nanjundan Meera M

Frontiers in oncology 20230417

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 cel ...[more]

PMID: 37139155

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Dataset Information

Deregulated Expression of the 14q32 miRNA Cluster in Clear Cell Renal Cell Carcinomas

Publications

Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells.

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