a Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
b Key Laboratory of Thyroid Tumor, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
Cancer Biol Ther. 2018 Jul 3;19(7):590-597. doi: 10.1080/15384047.2018.1449610. Epub 2018 May 3.
LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study.
Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133 cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively. MTT assay was performed to detect cytotoxicity. Chromatin immunoprecipitation was conducted to identify interactions between STAT3 and DNA promoter of INO80.
LncRNA PTCSC3 was low-expressed in ATC tissues and cells. Over-expressed PTCSC3 inhibited the drug resistance of ATC to doxorubicin. PTCSC3 negatively regulated STAT3, and STAT3 promoted expression of INO80. PTCSC3 regulated INO80 through STAT3. PTCSC3 suppressed stem cells properties and drug resistance of ATC to doxorubicin.
LncRNA PTCSC3 inhibits INO80 expression by negatively regulating STAT3, and thereby attenuating drug resistance of ATC to chemotherapy drug doxorubicin.
LncRNA PTCSC3 是甲状腺癌的肿瘤抑制因子，本研究探讨了其在甲状腺未分化癌（ATC）对化疗药物多柔比星耐药中的作用。
通过 qRT-PCR 和 Western blot 分别分析 RNA 和蛋白质的表达。通过流式细胞术分析 CD133 细胞的表达率。通过重组质粒和细胞转染调节相关基因的内源性表达。通过 RIP 和 RNA 下拉实验分别确定 PTCSC3 和 STAT3 之间的组合条件和相互作用。通过 MTT 测定法检测细胞毒性。通过染色质免疫沉淀鉴定 STAT3 与 INO80 DNA 启动子之间的相互作用。
LncRNA PTCSC3 在 ATC 组织和细胞中低表达。过表达 PTCSC3 抑制 ATC 对多柔比星的耐药性。PTCSC3 负调控 STAT3，STAT3 促进 INO80 的表达。PTCSC3 通过 STAT3 调节 INO80。PTCSC3 抑制 ATC 干细胞特性和多柔比星耐药性。
LncRNA PTCSC3 通过负调控 STAT3 抑制 INO80 的表达，从而减弱 ATC 对化疗药物多柔比星的耐药性。
