Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, PR China; Department of Pharmacy, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou 412007, PR China.
Department of Head and Neck Surgery and Oncology Plastic Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, CSU, Changsha 410006, PR China.
Biomed Pharmacother. 2020 Mar;123:109791. doi: 10.1016/j.biopha.2019.109791. Epub 2019 Dec 27.
SREBP1 is a well-known transcript factor regulating lipogenesis. It has been reported to play an important role in tumor progress in recent years. However, the roles of SREBP1 in differentiated thyroid cancer (DTC) are uncertain. Based on this, we aimed to investigate the expression of SREBP1 and the influence of SREBP1 on DTC patients.
qRT-PCR and immunohistochemistry were used to detect the expression of SREBPs in DTC tissues and the adjacent normal tissues. The following methods, including the MTS, colony-forming assay, flow cytometry and Hoechst staining were used to detect the biological function of thyroid cancer cells based on SREBP1 interference or not.
the expression of SREBP1 was significantly different among DTCs, thyroid nodules and the adjacent normal tissues. Briefly, SREBP1 was upregulated follow with the malignancy, but there was no significant difference of SREBP2 between thyroid nodules and the adjacent normal tissues. Further, the ROC curve showed that SREBP1 has higher diagnostic value than SREBP2. SREBP1 expression was significantly related to the tumor size and lymph node metastasis in DTCs. In vitro, the proliferation of thyroid cancer cells was suppressed obviously after interfered with SREBP1, and the apoptotic cells was increased. Further, SREBP1 expression was also associated with the short-term efficacy of levothyroxine in DTC patients.
this is the first time to report that SREBP1 is an oncogene and a pro-proliferation factor in thyroid cancer, indicating that SREBP1 may serve as a potential biomarker and therapeutic target in thyroid cancer.
SREBP1 是一种众所周知的调节脂肪生成的转录因子。近年来,它在肿瘤进展中的作用备受关注。然而,SREBP1 在分化型甲状腺癌(DTC)中的作用尚不确定。基于此,我们旨在研究 SREBP1 的表达及其对 DTC 患者的影响。
采用 qRT-PCR 和免疫组织化学法检测 DTC 组织及相邻正常组织中 SREBPs 的表达。采用 MTS、集落形成实验、流式细胞术和 Hoechst 染色等方法,检测 SREBP1 干扰或不干扰甲状腺癌细胞的生物学功能。
SREBP1 在 DTC、甲状腺结节和相邻正常组织中的表达存在显著差异。SREBP1 的表达随恶性程度的增加而上调,但 SREBP2 在甲状腺结节和相邻正常组织之间无明显差异。进一步的 ROC 曲线显示,SREBP1 的诊断价值高于 SREBP2。SREBP1 的表达与 DTC 中的肿瘤大小和淋巴结转移显著相关。体外实验显示,干扰 SREBP1 后甲状腺癌细胞的增殖明显受到抑制,凋亡细胞增多。此外,SREBP1 的表达也与 DTC 患者左甲状腺素短期疗效相关。
这是首次报道 SREBP1 是甲状腺癌中的癌基因和促增殖因子,表明 SREBP1 可能成为甲状腺癌潜在的生物标志物和治疗靶点。