Primary cilia are microtubule-based, dynamic organelles characterized by continuous assembly and disassembly. The intraflagellar transport (IFT) machinery, including IFT88 in cilia, is involved in the maintenance of bidirectional motility along the axonemes, which is required for ciliogenesis and functional competence. Cancer cells are frequently associated with loss of primary cilia and IFT functions. However, there is little information on the role of IFT88 or primary cilia in the metabolic remodeling of cancer cells. Therefore, we investigated the cellular and metabolic effects of the loss-of-function (LOF) mutations of IFT88/primary cilia in thyroid cancer cells. IFT88-deficient 8505C thyroid cancer cells were generated using the CRISPR/Cas9 system, and RNA-sequencing analysis was performed. LOF of the IFT88 gene resulted in a marked defect in ciliogenesis and mitochondrial oxidative function. Gene expression patterns in IFT88-deficient thyroid cancer cells favored glycolysis and lipid biosynthesis. However, LOF of IFT88/primary cilia did not promote thyroid cancer cell proliferation, migration, and invasion. The results suggest that IFT88/primary cilia play a role in metabolic reprogramming in thyroid cancer cells.

中文翻译：

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IFT88的功能丧失决定了甲状腺癌的代谢表型。

原发纤毛是基于微管的动态细胞器，其特征在于连续的组装和拆卸。鞭毛内运输（IFT）机械，包括纤毛中的IFT88，参与了沿纤毛的双向运动的维持，这是纤毛形成和功能能力所必需的。癌细胞通常与原发性纤毛和IFT功能丧失有关。但是，有关IFT88或原发性纤毛在癌细胞代谢重塑中的作用的信息很少。因此，我们调查了甲状腺癌细胞中IFT88 /原发纤毛的功能丧失（LOF）突变的细胞和代谢作用。使用CRISPR / Cas9系统生成IFT88缺陷型8505C甲状腺癌细胞，并进行RNA测序分析。IFT88基因的LOF导致睫毛发生和线粒体氧化功能的明显缺陷。IFT88缺陷型甲状腺癌细胞中的基因表达模式有利于糖酵解和脂质生物合成。但是，IFT88 /原发纤毛的LOF不会促进甲状腺癌细胞的增殖，迁移和侵袭。结果表明，IFT88 /原发纤毛在甲状腺癌细胞的代谢重编程中起作用。