化疗是晚期前列腺癌（PCa）的主要治疗手段，但药物敏感性存在个体差异。细胞自噬通过对细胞存亡的双向调控作用，参与调节PCa化疗敏感性，但具体效应及上游调控机制不清。MIIP是新抑癌基因，我们新近转录组测序表明MIIP影响细胞自噬过程。MIIP过表达PCa细胞中饥饿诱导的自噬标志分子变化更明显，且细胞对紫杉醇类药物更敏感。进一步，我们发现MIIP通过结合磷酸酶PP1并抑制 Akt/mTOR通路；并且MIIP下调miR-129-5p而上调其靶基因BECN1。这些强烈提示MIIP可能通过此两种方式调控细胞自噬，影响PCa化疗敏感性。据此，本项目拟利用PCa细胞系、裸鼠移植瘤和MIIPKO小鼠及临床组织样本，明确MIIP在细胞自噬中的作用，揭示MIIP调控自噬的分子机制，解析该调控在PCa化疗敏感性中的作用。本研究将丰富自噬调控理论，揭示MIIP新功能，并可能为基于自噬干预的PCa治疗提供依据。

Chemotherapy is the main treatment for metastatic prostate cancer (PCa), but there exists different chemosensitivity between individuals. Cell autophagy is involved in regulation of PCa chemosensivity through its two-sided regulation of cell survival and death., but the exact effect and the mechanism of the upstream regulation is still not clear. MIIP is a newly identified tumor suppressor. Our recent RNA-seq data indicated that MIIP influences the process of cell autophagy. MIIP-overexpressing PCa cells exhibited more obvious autophagy-marker alterations induced by starvation and were more sensitive to chemodrug taxanes than did the control cells. Moreover, we found that MIIP interacts with phosphatase PP1 and inhibits Akt/mTOR pathway. Meanwhile, MIIP downregulates miR-129-5p but upregualtes its target gene BECN1, which encodes well-known autophagy molecule Beclin-1. This suggested that MIIP can regulates cell autophagy through PP1/Akt/mTOR and miR-129-5p/Beclin-1, thereby influencing PCa chemosensitivity. In this project, by taking advantage of PCa cell lines, xenograft in nude mouse and MIIPKO mouse, as well as PCa samples, we will clarify the role of MIIP in cell autophagy, uncover the underlying mechanism through which MIIP regulates cell autophagy, elucidate the functional effect of such regulation in PCa chemosensitivity and finally, evaluate its clinical relevance. This study will enrich the theroy about autophagy regulation, reveal the novel MIIP function and may provide the evidence for autophagy-based treatment for PCa.