LncRNA-177922靶向MAPK15调节B16-F10黑色素瘤细胞黑色素生成、增殖、迁移和自噬(英文)

Regulation of LncRNA-177922 on Melanogenesis,Proliferation,Migration,and Autophagy of B16-F10 Melanoma Cells by Targeting MAPK15

黑色素瘤是一种预后较差的侵袭性癌症。了解黑色素瘤的分子机制和诊断标志物对黑色素瘤的防治极为重要。LncRNAs在肿瘤的发生发展中发挥重要作用。与正常黑色素细胞相比,LncRNA-177922在B16-F10黑色素瘤中高表达。丝裂源活化蛋白激酶15 (mitogen-activated protein kinase 15, MAPK15)的缺失影响肿瘤的发生和进展。本研究中,LncRNA-177922在B16-F10细胞中过表达,结果显示,黑色素生成、增殖、迁移相关基因的mRNA和蛋白质水平显著上调(P<0.05),自噬相关基因的mRNA水平和蛋白质丰度下调(P<0.05),PI3K/AKT/mTOR通路被激活。同时,进一步验证了细胞迁移、增殖和自噬的表型。结果提示,LncRNA-177922靶向MAPK15通过交叉点细胞外调节蛋白激酶(extracellular regulated protein kinases, ERK)参与调控黑色素生成、增殖、迁移、自噬等B16-F10细胞的生物学特性,可能是一个新的治疗靶点和诊断标志物。

Melanoma is an aggressive cancer with a poor prognosis. Understanding the molecular mechanism and diagnostic markers of melanoma is extremely important for the prevention and treatment of melanoma. LncRNAs play an important role in the genesis and progression of tumors. LncRNA-177922 was highly expressed in B16-F10 melanoma,compared with normal melanocytes. The loss of mitogenactivated protein kinase 15( MAPK15) affects tumor initiation and progression. Here,LncRNA-177922 was overexpressed in B16-F10 cells,and the results showed that the mRNA and protein of related-genes to melanogenesis,proliferation,and migration were significantly up-regulated( P < 0. 05),the mRNA levels and protein abundance of autophagy-related genes were down-regulated( P<0. 05),and the PI3 K/AKT/mT OR pathway was activated. Also,the phenotypes of cell proliferation,migration,and autophagy were further verified. The results suggested that LncRNA-177922 targeted MAPK15 in regulating the biological processes of B16-F10 cells such as melanogenesis,proliferation,migration,and autophagy through the cross-point extracellular regulated protein kinases( ERK),which might provide potential new therapeutic targets and diagnostic markers.