APOC2 Promotes Clear Cell Renal Cell Carcinoma Progression via Activation of the JAK-STAT Signaling Pathway

TL;DR

APOC2 promotes kidney cancer growth by activating the JAK-STAT pathway, suggesting it could be a new target for treatment.

Contribution

APOC2 is identified as a novel oncogenic regulator in ccRCC through JAK-STAT pathway activation.

Findings

APOC2 is upregulated in ccRCC and linked to poor prognosis.

APOC2 knockdown reduces cancer cell proliferation and activates apoptosis.

APOC2 promotes ccRCC progression via JAK-STAT pathway activation.

Abstract

This study aimed to investigate the role and underlying mechanism of apolipoprotein C2 (APOC2) in the progression of clear cell renal cell carcinoma (ccRCC). Analysis of The Cancer Genome Atlas (TCGA) datasets, combined with validation in ccRCC cell lines, revealed that APOC2 was markedly upregulated in ccRCC tissues and cells and was associated with poor patient prognosis. Functional assays demonstrated that APOC2 knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. Mechanistic studies showed that silencing APOC2 reduced the phosphorylation levels of key components of the JAK-STAT signaling pathway, including Jak1/2 and STAT3, without affecting their total protein expression. Gene enrichment analysis further indicated the involvement of JAK-STAT signaling, and functional rescue experiments using the STAT3 agonist Colivelin partially reversed the decreased cell viability and increased apoptosis caused by APOC2 knockdown, confirming the pathway’s mediating role. Collectively, these findings suggest that APOC2 promotes ccRCC cell proliferation and inhibits apoptosis, at least in part, through activation of the JAK-STAT signaling pathway, highlighting APOC2 as a novel oncogenic regulator and potential therapeutic target, and providing new insight into the metabolic–inflammatory axis in ccRCC progression. Clinically, APOC2 may serve as a biomarker to identify ccRCC patients with hyperactivated JAK-STAT signaling and could potentially guide combination therapies involving JAK/STAT inhibitors or metabolic-targeted agents.

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