# SOHLH2-RAD54L axis induces radioresistance by promoting homologous recombination repair in non-small cell lung cancer

## TL;DR

This study identifies a protein pathway that helps lung cancer cells resist radiation therapy, offering a new target for treatment.

## Contribution

The discovery of the SOHLH2-RAD54L axis as a novel mechanism promoting radioresistance in non-small cell lung cancer.

## Key findings

- SOHLH2 expression is elevated in non-small cell lung cancer and correlates with increased radioresistance.
- SOHLH2 activates RAD54L, which enhances homologous recombination repair and cancer cell survival after radiation.
- RAD54L overexpression can reverse the effects of SOHLH2 knockdown on radioresistance.

## Abstract

Radiation resistance is the major cause of non-small cell lung cancer (NSCLC) treatment failure. Homologous recombination (HR), which mediates the repair of DNA double-strand breaks (DSB), is crucial for maintaining genomic integrity and enhancing survival in response to radiotherapy in NSCLC. However, the mechanisms of HR repair in radiation resistance remains unclear. In this study, we investigated the functional role of the transcription factor Spermatogenesis and oogenesis basic helix-loop-helix transcription factor 2 (SOHLH2) in NSCLC HR repair and radioresistance. Our research unveiled that the expression levels of SOHLH2 increased in NSCLC compared with adjacent non-tumor tissues. Elevated SOHLH2 expression promotes NSCLC cell proliferation and radiation resistance, while knocking down SOHLH2 has the opposite effect. Mechanistically, SOHLH2 transcriptionally activated the expression of RAD54L, thereby promoting HR repair and the survival of cancer cells in response to radiation. Notably, RAD54L overexpression was able to rescue the suppression of NSCLC HR repair and radioresistance induced by SOHLH2 knockdown. Therefore, SOHLH2-RAD54L axis may serve as a potential therapeutic target for overcoming radioresistance in NSCLC.