Zheng Shiyi, Zhang Yi, Gong Xiaozhou, Teng Zhangyu, Chen Jun
Department of Cardiothoracic and Vascular Surgery, Guangyuan First People's Hospital, Guangyuan 628017, China.
J Clin Biochem Nutr. 2024 Sep;75(2):102-110. doi: 10.3164/jcbn.23-118. Epub 2024 Mar 22.
Mitophagy plays a vital role in carcinogenesis and tumor progression. However, the research on the mechanism of mitophagy in esophageal cancer metastasis is limited. This study explored the regulatory mechanism of RECQL4 in mitophagy and affects esophageal cancer metastasis. The RECQL4 expression in esophageal cancer tissues and cells was examined by bioinformatics and qRT-PCR. Bioinformatics analysis was used to determine the upstream regulatory factor of RECQL4 and CREB1. Their binding relationship was evaluated by dual luciferase and Chromatin Immunoprecipitation assays. The effects of RECQL4 on esophageal cancer cells viability, metastasis, and mitophagy were examined using CCK-8, Transwell, immunofluorescence, and Western blot assays. The expression of RECQL4 was up-regulated in esophageal cancer tissues and cells. Overexpression of RECQL4 promoted the cells viability, invasion, migration, and epithelial-mesenchymal transition by inhibiting mitophagy. Bioinformatics analysis revealed a positive correlation between RECQL4 and CREB1, their binding relationship was validatied by dual luciferase and ChIP assays. CREB1 knockdown promoted mitophagy and prevented the metastasis of cancer cells, which could be countered by overexpressing RECQL4. In conclusion, CREB1 was found to transcriptionally activate RECQL4 to inhibit mitophagy, thereby promoting esophageal cancer metastasis. Targeting mitophagy could be an effective therapeutic approach for esophageal cancer.
线粒体自噬在肿瘤发生和肿瘤进展中起着至关重要的作用。然而，关于线粒体自噬在食管癌转移机制方面的研究有限。本研究探讨了RECQL4在线粒体自噬中的调控机制及其对食管癌转移的影响。通过生物信息学和qRT-PCR检测食管癌组织和细胞中RECQL4的表达。利用生物信息学分析确定RECQL4和CREB1的上游调控因子。通过双荧光素酶和染色质免疫沉淀试验评估它们的结合关系。使用CCK-8、Transwell、免疫荧光和蛋白质免疫印迹试验检测RECQL4对食管癌细胞活力、转移和线粒体自噬的影响。RECQL4在食管癌组织和细胞中表达上调。RECQL4的过表达通过抑制线粒体自噬促进细胞活力、侵袭、迁移和上皮-间质转化。生物信息学分析显示RECQL4与CREB1呈正相关，双荧光素酶和染色质免疫沉淀试验验证了它们的结合关系。敲低CREB1可促进线粒体自噬并阻止癌细胞转移，而过表达RECQL4可抵消这种作用。总之，发现CREB1可转录激活RECQL4以抑制线粒体自噬，从而促进食管癌转移。靶向线粒体自噬可能是食管癌的一种有效治疗方法。
