放疗抵抗是影响前列腺癌临床整体疗效的主要因素之一，阐明其分子机制意义重大。NF-κB非经典通路转录因子RelB与前列腺癌放疗抵抗密切相关，但分子机制未明。我们前期工作首次发现RelB可能通过转录调控去乙酰化酶SIRT3参与氧化应激反应及DNA损伤修复，并发现DNA损伤修复关键蛋白NBS1可能是SIRT3潜在底物。我们由此推测RelB可能通过转录调控SIRT3抑制细胞氧化应激、促进DNA损伤修复诱导前列腺癌放疗抵抗。本研究拟通过体内及体外实验明确RelB-SIRT3信号通路诱导前列腺癌放疗抵抗的关键作用，进一步在分子水平揭示RelB转录调控SIRT3并激活SIRT3下游底物抑制细胞氧化应激、促进DNA损伤修复诱导前列腺癌放疗抵抗的分子机制，最后从临床角度探索RelB与前列腺癌放疗疗效及预后的关联，为未来寻找前列腺癌放疗增敏靶点及个体化治疗提供实验依据。

Radioresistence is one of the main factors which affect curative effect in prostate cancer. It is very meaningful to clarify the molecular mechanisms of radioresistence. Recent studies have demonstrated that RelB, the transcription factor of the noncanonical NF-κB pathway, is correlated with the radioresistance of prostate cancer, but the detailed mechanisms remain elusive. Our previous studies first demonstrated that RelB may transcriptionally regulate deacetylase SIRT3 in response to oxidative stress and DNA damage repair. Moreover, it was found that NBS1, a key DNA damage repair protein, might be a potential substrate of SIRT3. Thus, we hypothesize that RelB may induce radioresistence in prostate cancer by transcriptionally regulating SIRT3 which inhibits oxidative stress and promotes DNA damage repair. The study intents to verify the key role of RelB-SIRT3 signal pathway in prostate cancer radioresistence both in vitro and in vivo, then demonstrates the mechanisms of RelB in prostate cancer radioresistence by transcriptionally regulating SIRT3, then activating downstream substrates of SIRT3 which inhibit oxidative stress and enhance DNA damage repair. Finally, the study also tries to evaluate whether RelB expression is correlated with the radiotherapeutic effects and prognosis in clinical settings. This work will provide laboratory evidences for radiosensitive marker seeking and individualized treatments of prostate cancer in future.