Knockdown of ribosome RNA processing protein 15 (RRP15) suppresses metastasis of hepatocellular carcinoma via LAMC2/FAK pathway

Collectively, RRP15 is highly expressed in HCC tissues and is positively correlated with OS% and DSS% of HCC patients. Knockdown of RRP15 notably prevented the proliferation of HCC cells in vitro and the growth of ectopic transplanted tumors in vivo. Moreover, RRP15 knockdown suppressed the cells migration, invasion and adhesion through reducing the activation of laminin 5/integrin β4/FAK signaling pathway. The findings of the current study revealed the role of RRP15 in the progression of HCC, and laid a theoretical basis for RRP15 as a potential target for HCC diagnosis or/and treatment. The expression of RRP15 in normal liver tissues and HCC tissues were analyzed by using database. RT-qPCR, western blotting, proliferation assay, flow cytometry, transwell assay, cell scratch assay, cell adhesion assay and subcutaneous tumor-formation assay in nude mice were used to detect the effects of RRP15 on the proliferation, migration, invasion and adhesion of HCC cells. The underlying mechanism of RRP15 regulating the progression of HCC was further determined by RNA-seq and bioinformatics analysis.

总的来说，核糖体加工蛋白15（RRP15）在肝细胞癌（Hepatocellular Carcinoma, HCC）组织中高表达，且与肝细胞癌患者的总生存期（Overall Survival, OS）率及疾病特异性生存期（Disease-Specific Survival, DSS）率呈显著正相关。敲低RRP15可显著抑制肝细胞癌细胞的体外增殖，同时阻滞体内异位移植瘤的生长。此外，敲低RRP15可通过抑制层粘连蛋白5/整合素β4/黏着斑激酶（Focal Adhesion Kinase, FAK）信号通路的活化，削弱肝细胞癌细胞的迁移、侵袭与黏附能力。本研究结果阐明了RRP15在肝细胞癌进展中的作用，为将RRP15作为肝细胞癌诊断或治疗的潜在靶点提供了理论依据。本研究通过数据库分析了正常肝组织与肝细胞癌组织中RRP15的表达水平；采用实时定量聚合酶链反应（RT-qPCR）、蛋白质印迹法、增殖实验、流式细胞术、Transwell实验、细胞划痕实验、细胞黏附实验及裸鼠皮下成瘤实验，检测了RRP15对肝细胞癌细胞增殖、迁移、侵袭与黏附能力的影响；并通过RNA测序（RNA-seq）与生物信息学分析，进一步明确了RRP15调控肝细胞癌进展的潜在分子机制。