Ribosomal protein L8 promotes melanoma progression by regulating the cell cycle and metastasis

Abstract

Melanoma is an aggressive skin cancer with poor prognosis in advanced stages due to its metastatic potential. Although treatment modalities such as surgical resection, targeted therapy, immunotherapy, radiotherapy, and chemotherapy have conferred long-term survival benefits to certain patients, not all individuals respond favorably, underscoring the urgent need to develop predictive biomarkers. Ribosomal proteins have been implicated in tumor progression through extraribosomal functions. Ribosomal protein L8 (RPL8) is a unique ribosomal protein that warrants further exploration. Here, we investigated the role of RPL8 in melanoma progression. Using clinical data from the GDC and GEO databases, we found that high RPL8 expression is associated with poor prognosis in melanoma patients. Immunohistochemical analysis confirmed higher RPL8 expression in melanoma tissues compared to normal tissues. To elucidate the functional impact, we established an A875 melanoma cell line with stable RPL8 knockdown (shRPL8) using lentiviral vectors. RT-qPCR and western blot analysis confirmed efficient knockdown. CCK-8 assays showed that RPL8 knockdown significantly inhibited cell proliferation. Flow cytometry analysis revealed that RPL8 knockdown led to an increase in the proportion of cells in the G2/M phase and a decrease in the S phase, indicating cell cycle arrest. Furthermore, transwell assays demonstrated that RPL8 knockdown reduced cell invasion and migration. These findings suggest that RPL8 promotes melanoma progression by regulating the cell cycle and metastasis, and may serve as a potential therapeutic target and prognostic biomarker for melanoma.

1. Introduction

Melanoma is an aggressive skin cancer with poor prognosis in advanced stages due to its metastatic potential. In recent years, both the incidence and mortality rates of this disease have exhibited an upward trend [1]. Although treatment modalities such as surgical resection, targeted therapy, immunotherapy, radiotherapy, and chemotherapy have conferred long-term survival benefits to certain patients, not all individuals respond favorably [2,3]. This underscores the urgent need to develop predictive biomarkers to facilitate personalized and optimized therapeutic strategies.

The proliferation and division of tumor cells enhance ribosome biogenesis, and a growing body of evidence indicates that the dysregulation of certain ribosomal proteins is closely associated with tumor progression. Ribosomal proteins can be released from the ribosome in a free form and translocated to the nucleoplasm, where they exert extraribosomal functions. For instance, free ribosomal proteins can bind to MDM2 and activate P53 [4]. Extraribosomal functions of ribosomal proteins are involved in regulating various cellular processes, including the cell cycle, DNA repair, genomic integrity, cell proliferation, apoptosis, migration, and invasion [5,6]. Certain ribosomal proteins, such as RPS6 and RPSA, have been extensively investigated for their aberrant phosphorylation and correlation with melanoma progression and therapeutic resistance [7,8]. Ribosomal protein L8 (RPL8) is a unique ribosomal protein that warrants further exploration. As a component of the 60S large ribosomal subunit, RPL8 is integral to canonical ribosomal functions, including protein synthesis and RNA processing, and exhibits distinct extraribosomal regulatory roles. Emerging evidence suggests that RPL8 plays a significant role in melanoma biology by stimulating the clonal expansion of helper T cells (Th) and modulating the proliferation of lymphocytes or peripheral blood mononuclear cells (PBMCs), as well as cytokine expression, particularly interleukin-2 (IL-2) production, in patients with melanoma [9,10]. These findings underscore the potential of RPL8 as a key player in the anti-melanoma immune response, distinguishing it from other ribosomal proteins. Despite the growing recognition of ribosomal proteins in cancer research, the specific biological functions of RPL8 in melanoma tumorigenesis and progression remain poorly understood, making it a compelling target for novel investigations into its unique contributions to cancer biology.