NOP56 interacts with Fibrarin to regulate the PI3K/AKT signaling pathway and inhibit apoptosis of hepatocellular carcinoma

TL;DR

NOP56, a nucleolar protein, promotes liver cancer by interacting with fibrillarin and activating a key signaling pathway.

Contribution

NOP56's role in HCC progression via the NOP56–FBL–PI3K/AKT/CREB axis is newly identified.

Findings

NOP56 is upregulated in HCC and linked to poor prognosis.

NOP56 knockdown reduces tumor growth and activates apoptosis in HCC cells.

NOP56 interacts with fibrillarin to activate the PI3K/AKT/CREB pathway.

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. While *C-myc* is known to drive hepatocarcinogenesis, the roles of its downstream targets remain unclear. NOP56, a conserved nucleolar protein and *C-myc* target, may contribute to HCC progression.

We analyzed single-cell and bulk transcriptomic datasets to determine NOP56 expression and clinical significance. Loss-of-function assays in HCC cells, along with xenograft models, were used to evaluate its biological role. Protein interaction and pathway analyses were conducted using co-immunoprecipitation and Western blotting.

NOP56 was upregulated in malignant hepatocytes and associated with poor prognosis. NOP56 knockdown inhibited proliferation, colony formation, and migration, induced G0/G1 arrest and apoptosis, and reduced tumor growth in vivo. Mechanistically, NOP56 interacted with fibrillarin (FBL) and activated the PI3K/AKT/CREB pathway. Silencing NOP56 lowered FBL levels and suppressed pathway activity, whereas FBL overexpression partially rescued apoptotic effects.

NOP56 promotes HCC progression through the NOP56–FBL–PI3K/AKT/CREB axis. These findings reveal a previously unrecognized oncogenic role of nucleolar proteins in HCC and highlight this signaling axis as a promising therapeutic target.

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