Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo

Front Med. 2023 Feb;17(1):132-142. doi: 10.1007/s11684-022-0938-x. Epub 2022 Dec 23.

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.

Keywords: RFC4; WGCNA; nasopharyngeal carcinoma; proliferation.

MeSH terms

  • Carcinoma / genetics
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nasopharyngeal Carcinoma* / genetics
  • Nasopharyngeal Carcinoma* / metabolism
  • Nasopharyngeal Carcinoma* / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / pathology
  • Replication Protein C / genetics
  • Replication Protein C / metabolism

Substances

  • Replication Protein C
  • RFC4 protein, human
  • HOXA10 protein, human