Hu Wenjia, Wang Yan, Zhang Quanying, Luo Qianbing, Huang Ningxin, Chen Ran, Tang Xudong, Li Xiangyong, Luo Haiqing
Cancer Hospital of The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
Institute of Biochemistry and Molecular Biology of Guangdong Medical University, Zhanjiang 524023, China.
Cell Signal. 2023 Oct;110:110833. doi: 10.1016/j.cellsig.2023.110833. Epub 2023 Aug 4.
MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.
微小RNA（miR）是18 - 25个核苷酸的非编码RNA，其在肿瘤发生过程中发挥作用。先前的研究表明，miR - 199a - 3p在人类鼻咽癌（NPC）中表达失调，但其在NPC进展中的作用仍大多未知。当前研究旨在确定miR - 199a - 3p在NPC进展中的潜在作用及其潜在机制。在本研究中，发现miR - 199a - 3p在NPC组织和细胞中显著下调。细胞实验表明，转染miR - 199a - 3p可显著抑制5 - 8F和CNE - 2细胞系的迁移、侵袭并诱导上皮 - 间质转化（EMT）。通过双荧光素酶报告基因、蛋白质印迹和气相色谱分析，我们发现硬脂酰辅酶A去饱和酶1（SCD1）不仅在NPC组织中高表达且与NPC患者的预后呈负相关，而且在NPC细胞中可被miR - 199a - 3p明显下调，这表明SCD1是miR - 199a - 3p的直接靶基因。此外，抑制miR - 199a - 3p的表达可激活PI3K/Akt信号通路并上调基质金属蛋白酶2（MMP - 2）的表达。在裸鼠肿瘤异种移植模型中，我们还表明miR - 199a - 3p在体内可抑制肿瘤生长。我们的研究表明，miR - 199a - 3p通过下调SCD1的表达抑制NPC细胞的迁移和侵袭，从而为NPC的治疗提供了一个潜在靶点。
