Increased stemness is causally linked to development of drug resistance in cancers. JARID2 is a member of the Jumonji family of proteins and regulates differentiation of embryonic stem cells. However, the role of JARID2 in lung cancer stemness and drug resistance is still unclear. In this study, we investigated the expression of JARID2 in parental and cisplatin (CDDP) resistant non-small cell lung cancer (NSCLC) cells. The function of JARID2 in modulating CDDP sensitivity of NSCLC cells was determined. It was found that JARID2 is upregulated in CDDP resistant NSCLC cells, which depends on SOX2 expression. JARID2 overexpression promotes CDDP resistance in NSCLC cells, whereas JARID2 depletion restores CDDP sensitivity in CDDP resistant NSCLC cells. Moreover, JARID2 overexpression enhances cancer stem cell-like properties in NSCLC cells, which is coupled with increased expression of cancer stem cell markers. Mechanistically, JARID2-induced stemness and CDDP resistance is mediated by upregulation of Notch1. In clinical settings, high expression of JARID2 is significantly associated with advanced TNM stage, shorter overall survival, and poor chemotherapeutic response. These findings point toward an important role of JARID2 in CDDP resistance and stemness of NSCLC and provide a promising target for overcoming CDDP resistance.

增加的干性与癌症耐药性的发展有因果关系。JARID2 是 Jumonji 蛋白质家族的成员，调节胚胎干细胞的分化。然而，JARID2在肺癌干性和耐药性中的作用仍不清楚。在这项研究中，我们研究了 JARID2 在亲代和顺铂 (CDDP) 耐药的非小细胞肺癌 (NSCLC) 细胞中的表达。确定了 JARID2 在调节 NSCLC 细胞的 CDDP 敏感性中的功能。发现 JARID2 在 CDDP 抗性 NSCLC 细胞中上调，这取决于 SOX2 的表达。JARID2 过表达促进 NSCLC 细胞中的 CDDP 抗性，而 JARID2 消耗恢复 CDDP 抗性 NSCLC 细胞中的 CDDP 敏感性。此外，JARID2 过表达增强了 NSCLC 细胞中的癌症干细胞样特性，这与癌症干细胞标志物的表达增加相结合。从机制上讲，JARID2 诱导的干性和 CDDP 抗性是由 Notch1 的上调介导的。在临床环境中，JARID2 的高表达与晚期 TNM 分期、较短的总生存期和较差的化疗反应显着相关。这些发现表明 JARID2 在 CDDP 耐药性和 NSCLC 干性中的重要作用，并为克服 CDDP 耐药性提供了一个有希望的靶点。