RPP40, a subunit of Ribonuclease P, facilitates hepatocellular carcinoma proliferation by activating the mTOR/MYC...

Hepatocellular carcinoma (HCC) represents a major global health burden. While the ribonucleoprotein complex subunit RPP40 plays a critical role in precursor tRNA processing and has demonstrated prognostic value in several cancer types, its specific function and underlying mechanisms in HCC pathogenesis remain poorly understood.

Our comprehensive analysis utilized four independent datasets and one single-cell RNA sequencing dataset. Through integrated hallmark pathway enrichment analysis and drug repositioning studies, we screened and pinpointed the key pathway. Functional validation was performed using knockdown and overexpression approaches in Huh-7 and HepG2 cells, combined with in vitro experiments and subcutaneous xenograft tumor models in mice. Mechanistic exploration was subsequently carried out to elaborate the underlying regulatory mechanism.

Analysis showed that RPP40 expression was markedly upregulated in HCC tissues compared to adjacent normal tissues. High RPP40 expression correlated with poorer clinical outcomes, even among patients with matched histological grade or pathological stage. The mTOR/MYC signaling pathway was pinpointed as the key pathway regulated by RPP40 in HCC. RPP40 suppression attenuated cellular migration and proliferation, whereas its overexpression enhanced these malignant phenotypes both in vitro and in vivo. Mechanistic investigations established that RPP40 exerts its oncogenic effects through activation of the mTOR/MYC signaling pathway.

RPP40 promotes HCC proliferation and malignant behavior via activating the mTOR/MYC signaling pathway, which may serve as a potentially promising therapeutic target for HCC.