| Autor: |
Wang M; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China., Hu Y; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China., Cai F; Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China., Guo L; Department of Pathology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China., Mao Y; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China., Zhang Y; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China. |
| Abstrakt: |
Lung squamous cell carcinoma (LSCC) is a deadly cancer in the world. Histone demethylase Jmjd2c is a key epigenetic regulator in various tumors, while the molecular mechanism underlying Jmjd2c regulatory in LSCC is still unclear. We used the aldehyde dehydrogenasebright (ALDH bri+ ) subtype as a research model for cancer stem cells (CSCs) in LSCC and detected the sphere formation ability and the proportion of ALDH bri+ CSCs with Jmjd2c interference and caffeic acid (CA) treatment. Additionally, we carried out bioinformatic analysis on the expression file of Jmjd2c RNAi mice and performed western blotting, qRT-PCR, Co-IP and GST pull-down assays to confirm the bioinformatic findings. Moreover, we generated Jmjd2c-silenced and Jmjd2c-SOX2-silenced ALDH bri+ tumor-bearing BALB/c nude mice to detect the effects on tumor progression. The results showed that Jmjd2c downregulation inhibited the sphere formation and the proportion of ALDH bri+ CSCs. The SOX2 decreased expression significantly in Jmjd2c RNAi mice, and they were positively co-expressed according to the bioinformatic analysis. In addition, SOX2 expression decreased in Jmjd2c shRNA ALDH bri+ CSCs, Jmjd2c and SOX2 proteins interacted with each other. Furthermore, Jmjd2c interference revealed significant blocking effect, and Jmjd2c-SOX2 interference contributed even stronger inhibition on ALDH bri+ tumor progression. The Jmjd2c and SOX2 levels were closely related to the development and prognosis of LSCC patients. This study indicated that Jmjd2c played key roles on maintaining ALDH bri+ CSC activity in LSCC by interacting with transcription factor SOX2. Jmjd2c might be a novel molecule for therapeutic targets and biomarkers in the diagnosis and clinical treatment of lung cancer. |
