lncRNA NEAT1 facilitates melanoma cell proliferation, migration, and invasion via regulating miR-495-3p and E2F3
lncRNA NEAT1 facilitates melanoma cell proliferation, migration, and invasion via regulating miR-495-3p and E2F3
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DOI：
10.1002/jcp.28559
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Lin, Nengxing
中科院分区：
文献类型：
--
作者：
Xia, Ying;Zhou, Yu;Lin, Nengxing
黑色素瘤是导致皮肤癌相关死亡的主要原因。lncRNA与各种疾病有关，包括黑素瘤。lncRNA NEAT 1经常失调，并在多种癌症中发挥重要作用。然而，关于NEAT 1在黑色素瘤进展中的功能的研究很少。在我们目前的研究中，我们显示NEAT 1在黑色素瘤细胞中过表达。一系列的功能分析表明，NEAT 1的过表达促进了黑色素瘤细胞的增殖，迁移和侵袭。相比之下，NEAT 1敲低明显抑制黑色素瘤细胞的进展。从机制上讲，NEAT 1可以直接与miR-495- 3 p结合，这导致对miR-495- 3 p水平的负面影响。此外，miR-495- 3 p在黑素瘤细胞中显著降低。此外，E2 F3被假定为miR-495- 3 p的靶标，并且该miR的过表达可以抑制E2 F3的水平。同时，显示由E2 F3沉默诱导的黑素瘤细胞增殖、迁移和侵袭被miR-495- 3 p废除。此外，使用A375细胞建立体内异种移植裸鼠模型，并且表明NEAT 1通过调节miR-495- 3 p/E2 F3轴促进体内黑素瘤进展。总之，我们认为NEAT 1通过抑制miR-495- 3 p和诱导E2 F3对黑色素瘤的发展发挥致癌作用。NEAT 1可能是黑色素瘤的重要预后生物标志物。
Melanoma contributes a lot to skin cancer-related deaths. lncRNAs are implicated in various diseases, including melanoma. lncRNA NEAT1 is frequently dysregulated and can play important roles in multiple cancers. Nevertheless, little has been studied about the function of NEAT1 in melanoma progression. In our present research, we displayed NEAT1 was overexpressed in melanoma cells. A series of functional assays showed that overexpression of NEAT1 promoted the proliferation, migration, and invasion of melanoma cells. By contrast, NEAT1 knockdown obviously restrained melanoma cell progression. Mechanistically, it was revealed that NEAT1 could directly bind with miR-495-3p, which led to a negative effect on miR-495-3p levels. In addition, miR-495-3p was significantly decreased in melanoma cells. Furthermore, E2F3 was postulated as the target of miR-495-3p and overexpression of this miR could suppress the levels of E2F3. Meanwhile, it was exhibited that melanoma cell proliferation, migration, and invasion induced by E2F3 silence was abrogated by miR-495-3p. Moreover, an in vivo xenograft nude mice model was established using A375 cells and it was indicated that NEAT1 promoted melanoma progression in vivo via regulating the miR-495-3p/E2F3 axis. In conclusion, we suggest that NEAT1 exerts an oncogenic effect on melanoma development via inhibition of miR-495-3p and induction of E2F3. NEAT1 might serve as a crucial prognostic biomarker of melanoma.