Liu Zhengcheng, Zhao Wei, Yang Rusong
Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
Department of Biomedical Sciences and Tung Biomedical Sciences Centre, City University of Hong Kong, Kowloon, Hong Kong.
Environ Toxicol. 2022 Nov;37(11):2651-2659. doi: 10.1002/tox.23625. Epub 2022 Jul 27.
The stemness of lung cancer cells contributes to drug resistance, tumor occurrence, progression, and recurrence; however, the underlying mechanisms are still fragmentary. In the present study, it was found that exosomes from cisplatin-resistant cells and spheres derived from lung cancer cells enhanced the stemness of the parental lung cancer cells. Then we screened the upregulated miRNAs in spheres derived from lung cancer cells and cisplatin-resistant lung cancer cells/exosomes compared to that in the parental lung cancer cells. It was found that miR-1246 was remarkably enriched in cisplatin-resistant lung cancer cells/exosomes and spheres. Additionally, inhibition of miR-1246 attenuated the stemness of lung cancer cells induced by exosomes from cisplatin-resistant cells and spheres. Furthermore, TRIM17 was identified to the direct target of miR-1246 in lung cancer cells. Our findings suggest that exosomal miR-1246 could be as a potential target for lung cancer treatment.
肺癌细胞的干性导致耐药性、肿瘤发生、进展和复发;然而,其潜在机制仍不完整。在本研究中,发现来自顺铂耐药细胞的外泌体和源自肺癌细胞的球体增强了亲代肺癌细胞的干性。然后,我们筛选了与亲代肺癌细胞相比,源自肺癌细胞和顺铂耐药肺癌细胞/外泌体的球体中上调的miRNA。发现miR-1246在顺铂耐药肺癌细胞/外泌体和球体中显著富集。此外,抑制miR-1246可减弱顺铂耐药细胞和球体来源的外泌体诱导的肺癌细胞干性。此外,TRIM17被确定为肺癌细胞中miR-1246的直接靶点。我们的研究结果表明,外泌体miR-1246可能是肺癌治疗的潜在靶点。