Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma
Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma
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DOI：
10.1042/bsr20171031
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发表时间：
2017-12-22
影响因子：
4
通讯作者：
Sun, Weijing
中科院分区：
文献类型：
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作者：
Chen, Xiangjun;Liu, Sha;Sun, Weijing
黑色素瘤是最恶性的皮肤癌，占皮肤癌相关死亡的大部分。长链非编码RNA (lncRNA) 是一类在许多癌症中发挥关键作用的非编码RNA。然而，lncRNA 在黑色素瘤中的作用尚未得到充分研究。在本研究中，利用公开数据和临床组织样本，我们发现lncRNA ILF3-AS1在黑色素瘤组织和细胞系中表达上调，并且与黑色素瘤患者的不良预后相关。功能实验表明，ILF3-AS1 的敲低可抑制黑色素瘤细胞的增殖、迁移和侵袭。从机制上讲，我们发现ILF3-AS1与EZH2相互作用，促进EZH2与miR-200b/a/429启动子的结合，并抑制miR-200b/a/429的表达。黑色素瘤组织中ILF3-AS1的表达与miR-200b/a/429的表达呈负相关。此外，抑制 miR-200b/a/429 消除了 ILF3-AS1 敲低对黑色素瘤细胞增殖、迁移和侵袭的生物学作用。总之，这些结果表明黑色素瘤上调的lncRNA ILF3-AS1通过负向调节miR-200b/a/429促进细胞增殖、迁移和侵袭，并暗示ILF3-AS1可能是黑色素瘤的潜在预后生物标志物和治疗靶点。
Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.