The Affiliated Shenzhen Hospital, Anhui Medical University, Hefei, Anhui 230001, China.
Biomed Res Int. 2013;2013:251098. doi: 10.1155/2013/251098. Epub 2013 Jun 5.
Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level. While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis. The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.
转移性黑色素瘤是皮肤癌相关死亡的主要原因，需要新的治疗方法来靶向分子水平的调节机制。虽然长链非编码 RNA（lncRNA）在多种癌症类型中失调，但关于 lncRNA 在黑色素瘤转移中的表达和功能的有限数据。本研究的主要目的是研究 6 种与转移相关的 lncRNA 在配对的原发性黑色素瘤和匹配的淋巴结转移性组织中的作用。在测试的 lncRNA 中，HOTAIR 在淋巴结转移中表达最高。通过 siRNA 敲低 HOTAIR 进一步评估了 HOTAIR 在黑色素瘤细胞迁移和侵袭中的作用。通过划痕愈合试验和基于 Matrigel 的侵袭试验评估，敲低 HOTAIR 导致人黑色素瘤细胞系 A375 的迁移和侵袭减少。siHOTAIR 还抑制了明胶基质的降解，表明 HOTAIR 促进了明胶酶的活性。总之，我们的研究表明，HOTAIR 在转移性组织中过度表达，这与 HOTAIR 促进黑色素瘤细胞迁移和侵袭的能力有关。这些数据表明 lncRNA 可能参与黑色素瘤的转移，并为进一步评估 lncRNA 在黑色素瘤中的作用提供了支持。
