Department of Central Laboratory, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease.
Department of Oral Biology, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease.
Int J Med Sci. 2021 Sep 27;18(16):3728-3737. doi: 10.7150/ijms.64253. eCollection 2021.
Intrinsic or developing resistance to chemotherapy drugs including cisplatin (CDDP) remains the major limitation of cancer therapeutic efficacy in cancers. Recently, increasing evidence suggested that long noncoding RNAs (lncRNAs) play a critical role in various biological processes of tumors, and have been implicated in resistance to various drugs. However, the role of lncRNAs in cisplatin resistance is poorly understood. Here, we found that the expression of lncRNA CEBPA-DT/CEBPA/BCL2 was upregulated in cisplatin resistance OSCC cells (Cal27-CisR and HSC4-CisR) compared with their parental cells (Cal27 and HSC4). CEBPA-DT overexpression could upregulated both cytoplasmic and nuclear CEBPA expression. Down-regulation of CEBPA-DT enhances cisplatin sensitivity, facilitates cell apoptosis in cisplatin-resistant OSCC cells. In addition, we identified that CEBPA-DT regulates cisplatin chemosensitivity through CEBPA/BCL2-mediated cell apoptosis. Knockdown of CEBPA and BCL2 could alleviate the increasement of cisplatin resistance induced by CEBPA-DT overexpression. Our findings indicate that downregulation of lncRNA CEBPA-DT may be a potential therapy to overcome cisplatin resistance in OSCC.
内在或后天对化疗药物包括顺铂（CDDP）的耐药性仍然是癌症治疗疗效的主要限制因素。最近，越来越多的证据表明，长非编码 RNA（lncRNA）在肿瘤的各种生物学过程中发挥着关键作用，并与各种药物的耐药性有关。然而，lncRNA 在顺铂耐药性中的作用还知之甚少。在这里，我们发现与亲本细胞（Cal27 和 HSC4）相比，lncRNA CEBPA-DT/CEBPA/BCL2 的表达在顺铂耐药性 OSCC 细胞（Cal27-CisR 和 HSC4-CisR）中上调。CEBPA-DT 的过表达可以上调细胞质和核 CEBPA 的表达。下调 CEBPA-DT 可增强顺铂耐药性 OSCC 细胞的顺铂敏感性，促进细胞凋亡。此外，我们发现 CEBPA-DT 通过 CEBPA/BCL2 介导的细胞凋亡来调节顺铂的化疗敏感性。敲低 CEBPA 和 BCL2 可以减轻 CEBPA-DT 过表达引起的顺铂耐药性增加。我们的研究结果表明，下调 lncRNA CEBPA-DT 可能是克服 OSCC 中顺铂耐药性的一种潜在治疗方法。
