甲状腺乳头状癌自噬-上皮间质转化-铁死亡串扰调控机制的研究进展

Research progress on the crosstalk regulation mechanism among autophagy,epithelial-mesenchymal transformation and ferroptosis in papillary thyroid carcinoma

目的总结甲状腺乳头状癌(PTC)的自噬、上皮-间质转化(EMT)和铁死亡机制及其三者之间可能的串扰调控机制,探讨PTC高侵袭性、高复发性和高转移性的调控机制,为PTC的诊断和治疗提供新思路。方法以“甲状腺癌、自噬、上皮间质转化、铁死亡和串扰”为中文关键词,以“thyroid carcinoma、autophagy、epithelial-mesenchymal transition、ferroptosis、crosstalk”为英文关键词,在PubMed、中国知网数据库和万方数据库检索2012年1月-2022年6月发表的相关文献。共检索到中文文献170条,英文文献836条。纳入标准:(1)自噬、上皮间质转化和铁死亡及其串扰在PTC侵袭、复发和转移中的作用及机制;(2)甲状腺癌流行病学研究。排除标准:(1)研究机制不明文献;(2)会议论文、个案报道。根据标准纳入分析54篇文献。结果PTC进展中DNA突变引起基因表达改变,通过其他基因、miRNA和lncRNA直接或间接负向调控自噬,不但能够诱导EMT样变化,还可抑制铁死亡的发生,有助于癌细胞重新编程代谢途径和进行EMT,从而促进癌细胞的存活及其向其他器官转移。结论PTC中自噬与EMT、铁死亡三者间的串扰调控可能是促进PTC侵袭、转移和复发的重要调控机制。

Objective To explore the regulatory mechanism of high invasiveness,recurrence and metastasis of papillary thyroid carcinoma by briefly summarizing the mechanisms of autophagy,epithelial-mesenchymal transformation and ferroptosis and the possible crosstalk among them,so as to provide a new idea for the diagnosis and treatment for papillary thyroid carcinoma.Methods"Thyroid carcinoma,autophagy,epithelial-mesenchymal transition(EMT),iron death and crosstalk"were used as the Chinese and English keywords to search extensive literature in PubMed,CNKI database and Wanfang database and relevant literatures published in journals from January 2012to June 2022were included.A total of 170Chinese literatures and 836English literatures were retrieved.Inclusion criteria:(1)the role and mechanism of autophagy,epithelial stromal transformation,iron death and their crosstalk in PTC invasion,recurrence and metastasis;and(2)epidemiological study of thyroid cancer.Exclusion criteria:(1)documents with unclear research mechanism;and(2)conference papers,case reports.Totally 54literatures were included and analyzed according to the standard.Results DNA mutation cause gene expression changes during PTC progression.Autophagy is directly or indirectly negatively regulated by other genes,miRNA and lncRNA.It can not only induce EMT like changes,but also inhibit the occurrence of iron death.It is helpful for cancer cells to reprogram metabolic pathways and carry out EMT,thus promoting the survival of cancer cells and their metastasis to other organs.Conclusion The crosstalk regulation among the autophagy,epithelial-interstitial transformation and ferroptosis in papillary thyroid carcinoma may be an important regulatory mechanism to promote PTC invasion,metastasis and recurrence.