| Wen Yingren,Huang Jin,Yang Yuxin,et al.Mechanisms underlying HIST2H2BE lactylation in regulating radiation resistance in breast cancer cells[J].Chinese Journal of Radiological Medicine and Protection,2026,46(4):329-335 |
| Mechanisms underlying HIST2H2BE lactylation in regulating radiation resistance in breast cancer cells |
| Received:October 20, 2025 |
| DOI：10.3760/cma.j.cn112271-20251020-00365 |
| KeyWords:Breast cancer|Lactylation|Radiation resistance|HIST2H2BE |
| FundProject:国家自然科学基金(82574034);浙江省自然科学基金(LMS25H220002) |
| Author Name | Affiliation | E-mail | | Wen Yingren | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Huang Jin | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Yang Yuxin | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | | | Ma Shumei | School of Public Health, Wenzhou Medical University, Wenzhou 325035, China | shmm2001@126.com |
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| Abstract:: |
| Objective To investigate the role of the lactylation of histone H2B variant (HIST2H2BE) in regulating radiation resistance in breast cancer cells, along with the underlying mechanisms. Methods Differentially expressed genes (DEGs) were selected by analyzing the transcriptomic dataset GSE59733, which included pre- and post-radiotherapy data from breast cancer patients in the GEO database. Then, the intersection of DEGs and lactylation-related genes was determined. Based on experiments on the MCF-7 breast cancer cell line, changes in both overall lactylation levels of breast cancer cells and HIST2H2BE-specific lactylation were detected after ionizing radiation using Western blot. Potential lactylation sites were predicted using online tool DeepKla. Subsequently, key sites were validated using co-immunoprecipitation by constructing plasmids K31R, K44R, and K35R encoding lysine-to-arginine mutations. Cell viability and mortality were assessed using the CCK-8 and flow cytometry, respectively, to assess the effects of HIST2H2BE and its lactylation at site K35 on cellular radiosensitivity. Results HIST2H2BE exhibited high expression in breast cancer tissues and cells. Ionizing radiation induced both increased global lactylation levels of breast cancer cells and the specific promotion of HIST2H2BE lactylation, with K35 identified as the key lactylation site. Cell function experiments indicate that lactylation elimination by K35-to-K35R mutation led to reduced breast cancer cell viability (t =7.57, 8.91, P < 0.05) and significantly elevated radiation-induced cell mortality, indicating enhanced radiosensitivity (t =20.15, 49.46, P < 0.05) Conclusions The lactylation of HIST2H2BE at site K35 represents an important mechanism underlying radiation resistance in breast cancer cells. Therefore, targeted inhibition of such lactylation might serve as a potential strategy to reverse radiotherapy resistance in breast cancer. |
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