Department of Oncology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang.
Oncology Department, Xiangya Changde Hospital, Changde.
Anticancer Drugs. 2023 Jan 1;34(1):135-143. doi: 10.1097/CAD.0000000000001392. Epub 2022 Dec 2.
Nasopharyngeal carcinoma (NPC) is one of the most frequent malignant tumors diagnosed in China. Cisplatin is one of the most commonly used anticancer drugs containing platinum in combined chemotherapy. The molecular mechanism of NPC is still largely unknown, and we aim to spare no effort to elucidate it. Normal human nasopharyngeal epithelial cells and NPC cell lines were cultured. The expression levels of miR-302c-5p and HSP90AA1 were detected with quantitative real-time PCR. Western blotting was used to analyze levels of the HSP90AA1, protein kinase B (AKT), p-AKT, CD44 and SOX2 proteins. The interaction between miR-302c-5p and HSP90AA1 was detected using a luciferase reporter assay. The bicinchoninic acid assay was used to observe cisplatin resistance in NPC cells. Our records confirmed that the expression of miR-302c-5p was substantially reduced and HSP90AA1 was increased in NPC cells. Additionally, miR-302c-5p inhibited cisplatin resistance and the traits of stem cells in NPC. A luciferase assay confirmed that miR-302c-5p is bound to HSP90AA1. Overexpression of HSP90AA1 may reverse the effects of overexpressed miR-302c-5p and inhibit cisplatin resistance and stem cell traits of NPC. This study investigated whether miR-302c-5p inhibited the AKT pathway by regulating HSP90AA1 expression and altered the resistance of NPC cells to cisplatin and the traits of tumor stem cells, which has not yet been reported.
鼻咽癌（NPC）是中国最常见的恶性肿瘤之一。顺铂是最常用的含铂抗癌药物之一，用于联合化疗。NPC 的分子机制在很大程度上仍不清楚，我们旨在不遗余力地阐明它。培养正常的人鼻咽上皮细胞和 NPC 细胞系。用实时定量 PCR 检测 miR-302c-5p 和 HSP90AA1 的表达水平。用 Western blot 分析 HSP90AA1、蛋白激酶 B（AKT）、p-AKT、CD44 和 SOX2 蛋白的水平。用荧光素酶报告基因检测 miR-302c-5p 与 HSP90AA1 的相互作用。用二辛可宁酸法观察 NPC 细胞对顺铂的耐药性。我们的记录证实，miR-302c-5p 在 NPC 细胞中的表达显著降低，HSP90AA1 增加。此外，miR-302c-5p 抑制 NPC 中的顺铂耐药性和干细胞特性。荧光素酶测定证实 miR-302c-5p 与 HSP90AA1 结合。HSP90AA1 的过表达可能逆转过表达 miR-302c-5p 的作用，并抑制 NPC 中的顺铂耐药性和干细胞特性。本研究探讨了 miR-302c-5p 是否通过调节 HSP90AA1 表达抑制 AKT 通路，并改变 NPC 细胞对顺铂的耐药性和肿瘤干细胞特性，这尚未见报道。
