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

Abstract

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 PRDM5‐induced proliferation and invasion of B16F10 cells. To further verify the involvement of JNK signaling in PRDM5‐induced progression of B16F10 cells, a specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and results showed that PRDM5‐induced proliferation and invasion of B16F10 cells were abolished. We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression and strategies targeting PRDM5 may be promising for the therapy of melanoma.

Overexpression of PRDM5 promotes acute myeloid leukemia cell proliferation and migration by activating the JNK pathway

“…PRDM5 is generally implicated as a tumor suppressor in a variety of cancers due to the hypermethylation of its promoter . However, a recent study by Wang et al showed that PRDM5 acts as an important tumor promoter in the progression of malignant melanoma . Although PRDM5 has currently been studied in many cancers, the exact role and regulatory mechanism of PRDM5 in cancers are not completely understood.…”

“…The JNK pathway is a three‐tiered cascade. After activation, MAPKs phosphorylate specific serine and threonine residues on target substrates that in turn promotes tumor cell proliferation, migration and invasion . It has been reported that the JNK pathway activation promotes the proliferation of cancer cells by reducing the expression level of cell cycle inhibitors p16 or p21 .…”

“…Additionally, several studies have demonstrated that PRDM5 overexpression could induce cell cycle arrest and apoptosis in cancer cells . Moreover, Wang et al found that PRDM5 overexpression significantly promotes the proliferation and invasion of murine melanoma cells . These findings indicate that PRDM5 is involved in the regulation of hematopoiesis, cell differentiation, cell cycle, and apoptosis.…”

“…A recent study in melanoma suggests that suppressing JNK blocks PRDM5‐induced tumor progression . The JNK proteins (Jnk1, Jnk2, and Jnk3) are members of the mitogen‐activated protein kinase (MAPK) family and have been shown to exert controversial effects, acting either to mediate apoptosis or to sustain cell differentiation, proliferation, and tumorigenesis .…”

“…Moreover, the JNK signaling pathway has been widely implicated in cancer migration and metastasis. JNK inhibition mediated by the inhibitor SP600125 or specific siRNA impedes the growth of head and neck squamous cell carcinoma, melanoma, and myeloid leukemia …”