姜黄素调控长链非编码RNA MYOSLID增强头颈鳞癌细胞放疗敏感性的作用机制研究OA

Objective To investigate whether curcumin enhances the radiosensitivity of head and neck squamous cell carcinoma(HNSCC)by regulating the long non-coding RNA(lncRNA)MYOSLID and to elucidate the underlying mechanism.Methods LncRNA transcriptome sequencing combined with public datasets was used to identify key lncRNAs significantly altered by curcumin treatment.FaDu cells were divided into the following groups:control,radiation(RT),curcumin,curcumin plus RT(combination),and MYOSLID-overexpression combined with curcumin and RT.The expression of MYOSLID was measured by quantitative real-time poly-merase chain reaction(qRT-PCR).Cell proliferation,clonogenic survival,invasion,and apoptosis were assessed using Cell Counting Kit-8(CCK-8),colony formation,Transwell assays,and Annexin V/propidium iodide(PI)flow cytometry(FCM),respectively.West-ern blot(WB)was performed to detect the protein levels of γ-H2AX,phosphorylated ATM(p-ATM),phosphorylated CHK2(p-CHK2),and cleaved poly(ADP-ribose)polymerase(cleaved PARP)to evaluate changes in DNA damage and repair pathways.Results Bioinformatic screening identified MYOSLID as a key lncRNA downregulated by curcumin.qRT-PCR confirmed that both curcumin and RT reduced MYOSLID expression,with the most pronounced reduction observed in the combination treatment group(P<0.05).Either curcumin or RT alone inhibited the growth of FaDu cells,and the combination treatment resulted in the strongest inhibitory effect.Mechanistically,treatment with curcumin or RT alone increased the levels of γ-H2AX,cleaved PARP,p-ATM,and p-CHK2.The combination treatment further enhanced DNA damage(as indicated by increased γ-H2AX)and apoptosis,but showed a trend toward decreased p-ATM and p-CHK2 levels.Overexpression of MYOSLID partially reversed the growth inhibition caused by the combi-nation treatment,restored the levels of p-ATM and p-CHK2,and reduced γ-H2AX levels(P<0.05).Conclusion Curcumin downregu-lates MYOSLID,interferes with DNA damage repair processes,and augments radiation-induced DNA damage and apoptosis,thereby increasing the radiosensitivity of HNSCC.MYOSLID plays a critical role in this curcumin-mediated radiosensitization and may represent a potential therapeutic target.