基于TGF-β1/Smads通路研究马立克氏病病毒miR-M4对鸡CD4+T淋巴细胞增殖和恶性转化的影响

马立克氏病病毒（MDV）感染鸡后主要引起以CD4+T淋巴细胞增生为主的肿瘤性疾病，在前期研究中我们发现其编码的miR-M4在肿瘤发生发展过程中起着重要的调控作用,但其对CD4+T淋巴细胞增殖和恶性转化的调控作用及机制尚不清楚。因此，本研究拟在CD4+T淋巴细胞中异常表达miR-M4的基础上，检测miR-M4对鸡CD4+T淋巴细胞增殖和恶性转化的影响，同时在mRNA水平、蛋白水平检测TGF-β1/Smads信号通路关键信号分子的表达水平及活性变化，验证其与鸡CD4+T淋巴细胞增殖和恶性转化的相关性，明确miR-M4通过TGF-β1/Smads通路调控鸡CD4+T细胞增殖和恶性转化的作用机制。结果将为研究miR-M4的功能提供新的思路与途径，也为研究其他疱疹病毒miRNA调控宿主细胞肿瘤化的分子机制奠定理论基础。

Marek’s disease virus (MDV) is an herpesvirus that cause a neoplastic disease in chicken with the character of CD4+T cell lymphoma proliferative disorder. In the previous study, we found that the MDV1-miR-M4 had important regulative role in the tumorigenesis, however, the regulatory roles and mechanism of MDV miR-M4 in CD4+T lymphocyte proliferation and malignant transformation remain unknown. Therefore, the present study will examine the effect of MDV miR-M4 on the proliferation and malignant transformation of chickens CD4+T lymphocyte through the abnormal expression of miR-M4 in vitro. The changes of the expression and activity of the key signal molecules of TGF-β1/Smads, and the effects on the proliferation and malignant transformation of chickens CD4+T lymphocyte will also be studied. The mechanism of MDV-miR-M4 on the proliferation and malignant transformation of chickens CD4+T lymphocyte by the signal pathway of TGF-β1/Smads will be further illuminated. These findings will provide new evidence to research the role of miR-M4, and also provide theoretical basis to research the regulatory role of other herpesvirus miRNAs in host cells oncogenesis.