RPL35A Downregulation Suppresses Hepatocellular Carcinoma Cell Proliferation via NCAPG2 Inactivation

作者：Liang Chen, Yujie Lin, Yu Lai, Yanshan Li, Tao Chen, Xingxi Luo, Yibiao Ye · 发表于：Cancer Medicine · 年份：2025 · DOI：10.1002/cam4.70985 · 被引用次数：3 · 研究领域：RNA modifications and cancer、RNA and protein synthesis mechanisms、Ubiquitin and proteasome pathways

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying HCC progression remain poorly understood, prompting the need for novel therapeutic targets. RPL35A, a component of the 60S large ribosomal subunit, is a ribosomal protein involved in ribosome biogenesis and protein synthesis. Beyond its canonical role, increasing evidence suggests that ribosomal proteins such as RPL35A may also exert extraribosomal functions that contribute to tumorigenesis. METHODS: We investigated RPL35A expression in HCC using tissue samples and cell lines. RPL35A levels were correlated with clinicopathological features and prognosis in HCC patients. In vitro, we manipulated RPL35A expression in HCC cells using shRNA lentiviral vectors and assessed its effects on cell proliferation, migration and apoptosis. In vivo, we evaluated tumor growth using xenograft models. Gene expression analysis was conducted to identify downstream targets of RPL35A. RESULTS: RPL35A was significantly overexpressed in HCC tissues compared to normal liver, correlating with advanced disease stages and poorer prognosis. Knockdown of RPL35A in HCC cells inhibited cell proliferation, migration and invasion, while promoting apoptosis. In vivo, RPL35A silencing reduced tumor growth and size. Gene expression analysis identified NCAPG2 as a key downstream target of RPL35A. NCAPG2 expression was upregulated in HCC, and its knockdown reversed the oncogenic effe...