Study identifies RFC4 as key player in nasopharyngeal carcinoma

Frontiers JournalsJul 12 2024

Lichuan Wu et al., at Medical College of Guangxi University, China, presented a comprehensive study on the role of replication factor C subunit 4 (RFC4) in nasopharyngeal carcinoma (NPC), a type of epithelial cancer commonly associated with Epstein-Barr virus infection. The research was conducted with the aim of understanding the pathogenesis of NPC and identifying potential therapeutic targets.

NPC is a prevalent cancer in East and Southeast Asia, with over 133,000 new cases diagnosed in 2020 according to the International Agency for Research on Cancer (IARC). The main treatments for NPC include radiation therapy, concurrent chemoradiotherapy, and immune therapy. Despite improvements in the five-year overall survival rate, persistent and recurrent diseases are still a concern. The replication factor C (RFC) family proteins, including RFC4, are integral to DNA replication and repair processes. The study hypothesizes that RFC4 may have a significant role in NPC, a hypothesis that has not been explored in-depth previously.

The research utilized a multi-faceted approach involving bioinformatics analysis, cell culture, transfection assays, plate cloning formation assays, cell cycle detection, RNA extraction and real-time qPCR, RNA sequencing, western blot, and a nude mouse xenograft model. The study also included statistical analysis to measure the correlation between RFC4 and other genes, and to compare different experimental groups.

The study identified RFC4 as a potential key gene in NPC tumorigenesis through bioinformatics analysis, including weighted gene co-expression network analysis (WGCNA). The expression of RFC4 was found to be higher in NPC tumor tissues compared to normal tissues, as validated by immunohistochemical (IHC) assays. The knockdown of RFC4 in NPC cells led to the inhibition of cell proliferation and clone formation in vitro, and induced cell cycle arrest at the G2/M phase. The study also revealed that RFC4 regulates the expression of the homeobox transcription factor HOXA10, which is involved in cell differentiation and morphogenesis and has been implicated in various cancers.

The findings suggest that RFC4 may have an oncogenic role in NPC and that its mechanism of promoting cell proliferation might be distinct from other cancer types. The study also indicates that HOXA10 is a potential downstream target of RFC4, and that the overexpression of HOXA10 can partially reverse the inhibitory effects of RFC4 silencing on NPC cell proliferation. This implies that RFC4 may promote NPC cell proliferation by upregulating HOXA10.

The article provides a significant contribution to the understanding of NPC pathogenesis and offers a potential target for therapeutic intervention. The findings open avenues for future research into the specific mechanisms by which RFC4 regulates HOXA10 expression and its implications for NPC treatment.