BACKGROUND Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial-mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression. METHODS Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133+ cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133+ CSCs. RESULTS We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133+ cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133+ CSCs. CONCLUSIONS Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200b-regulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.

中文翻译：

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Pin2端粒重复因子1相互作用的端粒酶抑制剂1（PinX1）抑制鼻咽癌细胞的干性：对癌症的进展和治疗靶点的意义。

背景技术复发和远处转移仍然是导致包括鼻咽癌（NPC）在内的恶性肿瘤治疗失败的主要因素。因此，阐明鼻咽癌转移的分子机制对于靶向基因治疗和预后评估具有重要的临床意义。PinX1是一种抑癌基因，以前被证明是靶向端粒酶的强大工具，可以抵抗恶性肿瘤的增殖和迁移。这项研究的目的是探索PinX1调节NPC上皮-间质转化（EMT）和肿瘤转移的机制，并研究其在疾病进展中的临床意义和生物学作用。方法细胞计数试剂盒8（CCK8），Transwell分析，集落形成分析和异种移植物致瘤性测定用于测量鼻咽CD133 +癌症干细胞的增殖，迁移和侵袭能力。进行逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹试验，以研究PinX1通过调节鼻咽CD133 + CSCs中的EMT抑制细胞增殖，迁移和侵袭的潜在机制。结果我们发现在鼻咽CD133 +癌症干细胞（CSCs）中，PinX1和P53的过表达抑制了细胞的增殖，迁移和侵袭，但对miR-200b的抑制则阻止了这些作用。机理研究表明，PinX1通过调节P53 / miR-200b介导的Snail1，Twist1，Spin1的转录抑制来抑制细胞增殖，迁移和侵袭，和Zeb1，因此抑制了鼻咽CD133 + CSC中的EMT。结论我们的发现表明，PinX1在人NPC的恶性进展中通过P53 / miR-200b调控的EMT抑制细胞增殖，迁移和侵袭，这可能暗示了对疾病治疗的新的临床意义。