PDF(Pubmed)
Abstract：
In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.
摘要：
在这项研究中,我们研究了新发现的lncRNAFLJ20021在喉癌（LC）中的作用及其对顺铂治疗的耐药性。我们最初观察到在顺铂抗性LC细胞(Hep-2/R)中lncRNAFLJ20021水平升高。为了探索它的功能，我们将lncRNAFLJ20021和细胞周期蛋白依赖性激酶1（CDK1）转染到Hep-2/R细胞中，评估它们对顺铂敏感性和全景凋亡的影响。沉默lncRNAFLJ20021可有效降低Hep-2/R细胞中的顺铂耐药性并诱导PANoptosis。机械上,lncRNAFLJ20021主要位于细胞核中并与CDK1mRNA相互作用，从而增强其转录稳定性。CDK1，反过来，以ZBP1依赖性方式促进全细胞凋亡，这有助于克服Hep-2/R细胞的顺铂耐药性。这项研究表明，靶向lncRNAFLJ20021可以通过调节CDK1和通过ZBP1途径促进PANoptosis来对抗喉癌中的顺铂耐药性。这些发现为喉癌背景下基于lncRNA的治疗开辟了可能性。
