Exosomal miR-626 promotes the malignant behavior of oral cancer cells by targeting NFIB
Exosomal miR-626 promotes the malignant behavior of oral cancer cells by targeting NFIB
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DOI：
10.1007/s11033-022-07336-x
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发表时间：
2022-06
影响因子：
2.8
通讯作者：
Chao Lou;Jianbo Shi;Qin Xu
中科院分区：
文献类型：
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作者：
Chao Lou;Jianbo Shi;Qin Xu
背景肿瘤源性外泌体作为新兴的细胞间通讯调节因子，对于多种肿瘤的发生和发展具有重要意义。本研究的目的是探讨外泌体 miR-626 是否存在。更重要的是，如果外泌体miR-626存在，其转移到邻近癌细胞并促进肿瘤进展的机制需要阐明。方法和结果通过RT-qPCR分析miRNA和mRNA的表达。进行增殖、集落形成、伤口愈合、细胞周期来评估外泌体 miR-626 的功能。此外，利用异种移植实验来证实外泌体 miR-626 在口腔癌中的促癌作用。在这里，我们发现 miR-626 在口腔癌来源的外泌体中上调，并且可以在口腔癌细胞之间转移。外泌体 miR-626 促进癌细胞增殖、集落形成、迁移和 G0/G1-to-S 相转变。通过使用三种算法，预测核因子 I/B (NFIB) 是多种癌症中的肿瘤抑制基因，是 miR-626 的潜在靶标。荧光素酶报告基因检测数据显示，miR-626 可以直接结合 NFIB 的 3’-UTR，随后抑制其表达和下游信号传导。 NFIB 表达的恢复挽救了外泌体 miR-626 诱导的恶性表型。此外，外泌体miR-626的施用促进了异种移植肿瘤模型中的癌症生长，并伴随着NFIB表达的下调。结论我们的数据表明，外泌体miR-626可以通过抑制其靶标NFIB的表达来促进口腔癌的发展。外泌体 miR-626 可能是口腔癌的治疗靶点。
BackgroundTumor-derived exosomes, as emerging regulators of intercellular communication, are important for tumorigenesis and development in multiple tumors. The purpose of this study was to investigate whether exosomal miR-626 exists. More importantly, if exosomal miR-626 exists, the mechanism by which it is transferred into neighboring cancer cells and contributes to tumor progression needs to be clarified.Methods and ResultsThe expression of miRNA and mRNA are analyzed by RT-qPCR. Proliferation, colony formation, wound healing, cell cycle are carried out to assess the function of exosomal miR-626. Furthermore, a xenograft experiment is utilized to conform the cancer-promoting role of exosomal miR-626 in oral cancer. Here, we showed that miR-626 is upregulated in oral cancer–derived exosomes and can be transferred between oral cancer cells. Exosomal miR-626 promotes cancer cell proliferation, colony formation, migration and G0/G1-to-S phase transition. Nuclear factor I/B (NFIB), a tumor suppressor gene in various cancers, was predicted to be a potential target of miR-626 by using three algorithms. Luciferase reporter assay data revealed that miR-626 can directly bind to the 3’-UTR of NFIB and subsequently suppress its expression and downstream signaling. Restoration of NFIB expression rescued the malignant phenotype induced by exosomal miR-626. In addition, exosomal miR-626 administration facilitated cancer growth in a xenograft tumor model, accompanied by downregulation of NFIB expression.ConclusionsOur data demonstrate that exosomal miR-626 can facilitate the development of oral cancer by inhibiting the expression of its target NFIB. Exosomal miR-626 might be a therapeutic target for oral cancer.