肺鳞状细胞癌（LSCC）是世界上一种致命的癌症。组蛋白去甲基化酶 Jmjd2c 是多种肿瘤中关键的表观遗传调节因子，而 Jmjd2c 在 LSCC 中调节的分子机制尚不清楚。我们使用乙醛脱氢酶bright（ALDHbri）亚型作为LSCC中癌症干细胞（CSC）的研究模型，并检测Jmjd2c干扰和咖啡酸（CA）处理下的球体形成能力和ALDHbri CSC的比例。此外，我们对 Jmjd2c RNAi 小鼠的表达文件进行了生物信息学分析，并进行了蛋白质印迹、qRT-PCR、Co-IP 和 GST Pull-down 测定，以证实生物信息学结果。此外，我们还制备了 Jmjd2c 沉默和 Jmjd2c-SOX2 沉默 ALDHbri 荷瘤 BALB/c 裸鼠来检测对肿瘤进展的影响。结果表明，Jmjd2c 下调抑制了 ALDHbri CSCs 的球体形成和比例。 Jmjd2c RNAi小鼠中SOX2的表达显着降低，生物信息学分析显示它们呈阳性共表达。此外，Jmjd2c shRNA ALDHbri CSCs 中 SOX2 表达下降，Jmjd2c 和 SOX2 蛋白相互作用。此外，Jmjd2c干扰显示出显着的阻断作用，并且Jmjd2c-SOX2干扰对ALDHbri肿瘤进展具有更强的抑制作用。 Jmjd2c、SOX2水平与LSCC患者的病情发展及预后密切相关。这项研究表明，Jmjd2c 通过与转录因子 SOX2 相互作用，在维持 LSCC 中 ALDHbri CSC 活性方面​​发挥着关键作用。 Jmjd2c可能是肺癌诊断和临床治疗中治疗靶点和生物标志物的新型分子。

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 (ALDHbri+) subtype as a research model for cancer stem cells (CSCs) in LSCC and detected the sphere formation ability and the proportion of ALDHbri+ 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 ALDHbri+ 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 ALDHbri+ 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 ALDHbri+ 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 ALDHbri+ 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 ALDHbri+ 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.