Abstract：
BACKGROUND: Thyroid cancer is a rare but increasingly prevalent form of cancer worldwide. The development and progression of thyroid cancer are associated with mitochondrial instability, which refers to alterations in the structure, function, and energy status of mitochondria. These alterations lead to an imbalance in mitochondrial metabolism, causing cellular damage and apoptosis. However, the molecular mechanisms underlying mitochondrial instability and thyroid cancer remain poorly understood.
OBJECTIVE: This study aimed to explore the molecular mechanism of delaying the progression of thyroid cancer by regulating mitochondrial homeostasis through fumarate 1-mediated PGC-1α in vitro.
METHODS: Human papillary thyroid carcinoma cell lines (TPC-1 and K-1) and a normal thyroid cell line (Nthy-ori 3-1) were cultured in this study. TPC-1 cells and K-1 cells were separately transfected with oveRNA-FH1 and oveRNA-NC, designated as the oveRNA-FH1 group, oveRNA- NC group, TPC-1 group, and Nthy-ori 3-1 group. Various assays were performed to assess cell viability, proliferation capacity, invasion and migration abilities, as well as mitochondrial morphology changes and the expression of relevant factors. qRT-PCR and Western blot analysis were carried out to analyze the expression changes of PGC-1α, mitochondrial dynamics-related factors, and pyroptosis genes. The goal of these experiments was to evaluate the impact of FH1 on mitochondrial instability and elucidate the specific mechanisms underlying thyroid cancer and mitochondrial instability.
RESULTS: The results of this study demonstrated that FH1 expression was significantly downregulated in thyroid papillary carcinoma cell lines compared to the normal thyroid cell line. Overexpression of FH1 reduced cell viability and inhibited cell proliferation rate in TPC-1 cells. Furthermore, FH1 overexpression suppressed cell invasion and migration abilities. Abnormal mitochondrial morphological changes were observed in TPC-1 and K-1 cells, whereas FH1 overexpression resulted in relatively normal mitochondria. FH1 overexpression also affected the expression of fusion and fission genes, promoting fission and inhibiting fusion in thyroid cancer cells. Moreover, FH1 overexpression led to increased inflammation and pyroptosis. These conclusions were further verified by in vitro tumor formation experiments.
CONCLUSIONS: FH1 promoted thyroid cancer progression by regulating mitochondrial homeostasis via the PGC-1α-dependent pathway, which affected pyroptosis and apoptosis.
OBJECTIVE: This study aimed to explore the molecular mechanism of delaying the progression of thyroid cancer by regulating mitochondrial homeostasis through fumarate 1-mediated PGC-1α in vitro.
METHODS: Human papillary thyroid carcinoma cell lines (TPC-1 and K-1) and a normal thyroid cell line (Nthy-ori 3-1) were cultured in this study. TPC-1 cells and K-1 cells were separately transfected with oveRNA-FH1 and oveRNA-NC, designated as the oveRNA-FH1 group, oveRNA- NC group, TPC-1 group, and Nthy-ori 3-1 group. Various assays were performed to assess cell viability, proliferation capacity, invasion and migration abilities, as well as mitochondrial morphology changes and the expression of relevant factors. qRT-PCR and Western blot analysis were carried out to analyze the expression changes of PGC-1α, mitochondrial dynamics-related factors, and pyroptosis genes. The goal of these experiments was to evaluate the impact of FH1 on mitochondrial instability and elucidate the specific mechanisms underlying thyroid cancer and mitochondrial instability.
RESULTS: The results of this study demonstrated that FH1 expression was significantly downregulated in thyroid papillary carcinoma cell lines compared to the normal thyroid cell line. Overexpression of FH1 reduced cell viability and inhibited cell proliferation rate in TPC-1 cells. Furthermore, FH1 overexpression suppressed cell invasion and migration abilities. Abnormal mitochondrial morphological changes were observed in TPC-1 and K-1 cells, whereas FH1 overexpression resulted in relatively normal mitochondria. FH1 overexpression also affected the expression of fusion and fission genes, promoting fission and inhibiting fusion in thyroid cancer cells. Moreover, FH1 overexpression led to increased inflammation and pyroptosis. These conclusions were further verified by in vitro tumor formation experiments.
CONCLUSIONS: FH1 promoted thyroid cancer progression by regulating mitochondrial homeostasis via the PGC-1α-dependent pathway, which affected pyroptosis and apoptosis.
摘要：
背景：甲状腺癌是世界范围内罕见但日益普遍的癌症。甲状腺癌的发生发展与线粒体不稳定有关,指的是结构的改变，函数,和线粒体的能量状态。这些改变导致线粒体代谢失衡，引起细胞损伤和凋亡。然而,线粒体不稳定和甲状腺癌的分子机制仍然知之甚少.
目的：本研究旨在探讨延胡索酸1介导PGC-1α体外调控线粒体稳态延缓甲状腺癌进展的分子机制。
方法：本研究培养人甲状腺乳头状癌细胞系（TPC-1和K-1）和正常甲状腺细胞系（Nthy-ori3-1）。分别用oveRNA-FH1和oveRNA-NC转染TPC-1细胞和K-1细胞,指定为OveRNA-FH1组，OveRNA-NC组，TPC-1组,还有Nthy-ori3-1组.进行各种测定以评估细胞活力，增殖能力,入侵和迁移能力，以及线粒体形态变化和相关因子的表达。采用qRT-PCR和Westernblot分析PGC-1α的表达变化,线粒体动力学相关因子，和焦亡基因。这些实验的目的是评估FH1对线粒体不稳定性的影响，并阐明甲状腺癌和线粒体不稳定性的具体机制。
结果：这项研究的结果表明，与正常甲状腺细胞系相比，FH1在甲状腺乳头状癌细胞系中的表达显着下调。在TPC-1细胞中,FH1的过表达降低细胞活力并抑制细胞增殖速率。此外，FH1过表达抑制细胞侵袭和迁移能力。TPC-1和K-1细胞线粒体形态异常改变,而FH1过表达导致相对正常的线粒体。FH1过表达也影响融合和裂变基因的表达，促进甲状腺癌细胞的裂变和抑制融合。此外，FH1过表达导致炎症和焦亡增加。这些结论通过体外成瘤实验得到进一步验证。
结论：FH1通过PGC-1α依赖性途径调节线粒体稳态促进甲状腺癌进展，影响焦亡和细胞凋亡。
目的：本研究旨在探讨延胡索酸1介导PGC-1α体外调控线粒体稳态延缓甲状腺癌进展的分子机制。
方法：本研究培养人甲状腺乳头状癌细胞系（TPC-1和K-1）和正常甲状腺细胞系（Nthy-ori3-1）。分别用oveRNA-FH1和oveRNA-NC转染TPC-1细胞和K-1细胞,指定为OveRNA-FH1组，OveRNA-NC组，TPC-1组,还有Nthy-ori3-1组.进行各种测定以评估细胞活力，增殖能力,入侵和迁移能力，以及线粒体形态变化和相关因子的表达。采用qRT-PCR和Westernblot分析PGC-1α的表达变化,线粒体动力学相关因子，和焦亡基因。这些实验的目的是评估FH1对线粒体不稳定性的影响，并阐明甲状腺癌和线粒体不稳定性的具体机制。
结果：这项研究的结果表明，与正常甲状腺细胞系相比，FH1在甲状腺乳头状癌细胞系中的表达显着下调。在TPC-1细胞中,FH1的过表达降低细胞活力并抑制细胞增殖速率。此外，FH1过表达抑制细胞侵袭和迁移能力。TPC-1和K-1细胞线粒体形态异常改变,而FH1过表达导致相对正常的线粒体。FH1过表达也影响融合和裂变基因的表达，促进甲状腺癌细胞的裂变和抑制融合。此外，FH1过表达导致炎症和焦亡增加。这些结论通过体外成瘤实验得到进一步验证。
结论：FH1通过PGC-1α依赖性途径调节线粒体稳态促进甲状腺癌进展，影响焦亡和细胞凋亡。
