Hong Yuming, Chen Xiaofang, Liang Zhenyuan, Xu Zhihui, Li Yahong, Pan Yafeng
Department of Otolaryngology, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian, China.
Anticancer Drugs. 2020 Oct;31(9):925-931. doi: 10.1097/CAD.0000000000000919.
Studies have confirmed that microRNAs play important roles in the development and progression of cancer. Therefore, to identify the differentially expressed microRNAs between the cancer and the normal tissues, microRNAs will provide new clues for exploring the molecular mechanisms of cancer development and potential targeted therapies. In the present study, we found that miR-338-3p was downregulated in hypopharyngeal carcinoma and inversely correlated with the pathological grade. When the miR-338-3p was further downregulated, the migration and invasion ability of the FaDu hypopharyngeal carcinoma cells were enhanced, and these functions were inhibited when the miR-338-3p was upregulated. In addition, we demonstrated that ADAM17 was a target of miR-338-3p, and that ADAM17 directly activated the wnt/β-catenin signaling pathway and promoted the expression of its target gene MMP2, Nanog and SOX2, which affected the growth, migration and invasion of hypopharyngeal carcinoma cells. In conclusion, our results demonstrate for the first time that miR-338-3p targets ADAM17 and blocks the development of hypopharyngeal carcinoma involving the wnt/β-catenin signaling pathway, which may be a new target for clinical intervention in human cancer.
研究已证实，微小RNA在癌症的发生发展过程中发挥着重要作用。因此，为了鉴定癌症组织与正常组织之间差异表达的微小RNA，微小RNA将为探索癌症发生的分子机制和潜在的靶向治疗提供新线索。在本研究中，我们发现miR-338-3p在下咽癌中表达下调，且与病理分级呈负相关。当miR-338-3p进一步下调时，FaDu下咽癌细胞的迁移和侵袭能力增强，而当miR-338-3p上调时，这些功能受到抑制。此外，我们证明ADAM17是miR-338-3p的一个靶点，ADAM17直接激活wnt/β-连环蛋白信号通路并促进其靶基因MMP2、Nanog和SOX2的表达，从而影响下咽癌细胞的生长、迁移和侵袭。总之，我们的结果首次表明，miR-338-3p靶向ADAM17并阻断涉及wnt/β-连环蛋白信号通路的下咽癌发展，这可能是人类癌症临床干预的一个新靶点。
