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PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression

机译:PRDM5通过上调JNK表达促进鼠黑色素瘤细胞的增殖和侵袭

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摘要

PRDM (PRDI‐BF1 and RIZ domain‐containing) proteins constitute a family of zinc finger proteins and play important roles in multiple cellular processes by acting as epigenetic modifiers. PRDM5 is a recently identified member of the PRDM family and may function as a tumor suppressor in several types of cancer. However, the role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of PRDM5 on murine melanoma cells was determined and results showed that PRDM5 overexpression significantly promoted proliferation, migration, and invasion of murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression significantly inhibited proliferation, invasion, and migration of B16F10 cells. In vivo study also showed that PRDM5 silencing significantly inhibited the growth and metastasis of melanoma in mice. PRDM5 was then found to increase the expression and activation of JNK in B16F10 cells. JNK silencing significantly reduced PRDM5‐mediated up‐regulation of JNK expression and blocked the style="fixed-case">PRDM5‐induced proliferation and invasion of B16F10 cells. To further verify the involvement of style="fixed-case">JNK signaling in style="fixed-case">PRDM5‐induced progression of B16F10 cells, a specific style="fixed-case">JNK inhibitor was employed to inhibit the style="fixed-case">JNK signaling pathway, and results showed that style="fixed-case">PRDM5‐induced proliferation and invasion of B16F10 cells were abolished. We conclude that style="fixed-case">PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating style="fixed-case">JNK expression and strategies targeting style="fixed-case">PRDM5 may be promising for the therapy of melanoma.
机译:PRDM(含PRDI-BF1和RIZ域)蛋白构成锌指蛋白家族,并通过充当表观遗传修饰剂在多个细胞过程中发挥重要作用。 PRDM5是PRDM家族中最近被鉴定的成员,可能在多种类型的癌症中起抑癌作用。然而,PRDM5在鼠类黑色素瘤中的作用仍然未知。在我们的研究中,确定了PRDM5对鼠类黑色素瘤细胞的作用,结果表明PRDM5的过表达显着促进了鼠类黑色素瘤B16F10细胞的增殖,迁移和侵袭。一致地,PRDM5表达的沉默显着抑制B16F10细胞的增殖,侵袭和迁移。体内研究还表明,PRDM5沉默可显着抑制小鼠黑色素瘤的生长和转移。然后发现PRDM5增加了B16F10细胞中JNK的表达和激活。 JNK沉默可显着降低PRDM5介导的JNK表达上调,并阻止 style =“ fixed-case”> PRDM 5诱导的B16F10细胞增殖和侵袭。为了进一步验证 style =“ fixed-case”> JNK 信号在 style =“ fixed-case”> PRDM 5诱导的B16F10细胞进展中的参与,特定的采用style =“ fixed-case”> JNK 抑制剂抑制 style =“ fixed-case”> JNK 信号通路,结果表明 style =“ fixed-case” > PRDM 5诱导的B16F10细胞增殖和侵袭被消除。我们得出结论, style =“ fixed-case”> PRDM 5通过上调 style =“ fixed-case”> JNK 的表达和策略促进鼠黑色素瘤细胞的增殖和侵袭。靶向 style =“ fixed-case”> PRDM 5有望用于治疗黑色素瘤。

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