ESTRO meets Asia 2024 - Abstract Book

S256

Interdisciplinary – Radiobiology

ESTRO meets Asia 2024

376

Digital Poster

m6A methylation regulates the invasion decrease of radiation-resistant hepatocellular carcinoma

Zhi-Feng Wu

Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

Purpose/Objective:

The aim of this study was to investigate the mechanisms underlying recurrence and metastasis after radiotherapy for liver cancer, with a focus on the role of RNAm6A methylation in regulating invasion and metastasis of radiation tolerant liver cancer cells.

Material/Methods:

Liver cancer cell line (97H) surviving after 6Gy-X-ray irradiation was used. Cell radiosensitivity was assessed through clone formation experiments and nude mice subcutaneous tumor radiotherapy. YTHDF2 gene low expression cell line (97H_sh_Ythdf2) was constructed using RNAi technology. Invasion and metastasis ability of HCC cells were evaluated through scratch experiments, Transwell experiments, and nude mice liver tumor in situ experiments. mRNA m6A methylation was detected using MeRIP-seq technology.

Results:

Radiation-tolerant HCC cell line (97H-RS) was successfully induced by 3 rounds of 6Gy-X-ray irradiation. Clone formation experiment and nude mice subcutaneous tumor radiotherapy confirmed its radioresistance characteristics. Scratch experiment, Transwell experiment, and nude mice liver tumor in situ experiment demonstrated that both 97H-RS and 97H_sh_Ythdf2 cell lines exhibited inhibited invasion and metastasis compared to the control group. A total of 65 genes showed significant changes in RNA expression and m6A modification in both cell lines, with only LOXL4 and VCAM1 found to be associated with inhibiting invasion and metastasis of liver cancer cells.

Conclusion:

The invasion and metastasis ability of radiation-tolerant HCC cells was significantly decreased. Inhibition of YTHDF2 and modification of m6A methylation of LOXL4, VCAM1 and other proteins are the regulatory mechanisms of invasion and metastasis inhibition.

Keywords: m6A, HCC, radiation-resistance

465

Digital Poster