INSM1在静默性促肾上腺皮质激素细胞腺瘤发生发展中的调控机制及潜在靶向治疗研究

静默性促肾上腺皮质激素细胞腺瘤（SCA）相比其他类型的垂体神经内分泌肿瘤（PitNET）具有更高的复发可能性，常呈现出侵袭性生长的特点，经过手术和放疗后仍无法控制肿瘤生长，预后差。但是，SCA在最新一版WHO分类中提出至今仅4年时间，对其研究存在明显不足。INSM1在神经内分泌细胞分化的发生发展中起重要作用。我们的前期研究发现，INSM1在SCA中异常高表达，可以促进SCA的发生发展，提示INSM1可能是SCA侵袭性等生物学行为的分子基础。本课题针对目前INSM1在PitNET中功能和作用机制不明确的现状，以“INSM1是否以及如何调控SCA发生发展”为核心，拟解决以下关键科学问题：1、INSM1在转录水平和核外信号通路水平调控SCA发生发展的具体机制如何？ 2、造成INSM1在SCA中特异性高表达的分子机制是什么？3、INSM1及其调控通路成员是否在SCA的治疗中具有应用价值？

Silent adrenocorticotropic cell adenoma (SCA) is more likely to recur than other types of pituitary neuroendocrine tumors (PitNET). It often presents the characteristics of invasive growth. After surgery and radiotherapy, the tumor growth can not be controlled and the prognosis is poor. However, it is only four years since SCA was put forward in the latest edition of WHO classification. INSM1 plays an important role in the development of neuroendocrine cell differentiation. Our previous study found that INSM1 is highly expressed in SCA, which can promote the occurrence and development of SCA, suggesting that INSM1 may be the molecular basis of SCA invasion and other biological behaviors. In view of the current situation that the function and mechanism of INSM1 in PitNET are not clear, this project aims to solve the following key scientific problems with the core of "whether and how INSM1 regulates the occurrence and development of SCA": 1. What is the specific mechanism of INSM1 in regulating the occurrence and development of SCA at transcriptional level and extracellular signal pathway level? 2. What is the molecular mechanism of INSM1 overexpression in SCA? 3. Are INSM1 and its regulatory pathway members valuable in the treatment of SCA?