RFC5 enhances DNA damage response and immune escape via suppressing the cGAS-STING pathway in nasopharyngeal

Yumo Han1, Mengyu Miao2, Ying Shan1

  • 1Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong 226001, China; Medical School, Nantong University, Qixiu Road 19, Nantong 226001, China; Department of Otorhinolaryngology Head and Neck surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong 226001, China.

Cellular Signalling
|November 5, 2025
PubMed

Insights

High RFC5 expression in nasopharyngeal carcinoma (NPC) promotes DNA repair and immune evasion, hindering chemotherapy and radiotherapy effectiveness. Targeting RFC5 could improve cancer treatment outcomes.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Tumor cell DNA repair capacity correlates with resistance to radio/chemotherapy.
  • Nasopharyngeal carcinoma (NPC) exhibits resistance to conventional cancer treatments.

Purpose of the Study:

  • To investigate the role of RFC5 in DNA damage repair and immune evasion in NPC.
  • To explore RFC5 as a potential therapeutic target for enhancing cancer treatment.

Main Methods:

  • Assessed RFC5 expression in NPC cells.
  • Conducted mechanistic studies on DNA damage repair and cGAS-STING signaling.
  • Performed in vivo experiments to evaluate immune microenvironment changes and T cell exhaustion.

Main Results:

  • Elevated RFC5 expression in NPC cells enhances DNA repair, reducing cisplatin-induced DNA damage and micronuclei formation.
  • High RFC5 suppresses cGAS-STING signaling, inflammatory mediator production, and promotes tumor progression.
  • RFC5 overexpression leads to reduced IFN-γ and TNF-α secretion, increased PD-1, LAG-3, CTLA-4 expression, and T cell exhaustion in vivo.

Conclusions:

  • RFC5 facilitates cisplatin-induced DNA damage repair and promotes immune evasion in NPC.
  • RFC5 is a potential therapeutic target for overcoming treatment resistance and enhancing outcomes in radiotherapy and chemotherapy.

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.0K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.2K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.0K