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Abstract:
Dual-specificity phosphatase 8 (DUSP8) plays an important role as a
selective c-Jun N-terminal kinase (JNK) phosphatase in mitogen-activated
protein kinase (MAPK) signaling. In this study, we found that DUSP8 is
silenced by miR-147b in patients with lung adenocarcinoma (LUAD), which
correlates with poor overall survival. Overexpression of DUSP8 resulted
in a tumor-suppressive phenotype in vitro and in vivo experimental
models, whereas silencing DUSP8 with a siRNA approach abrogated the
tumor-suppressive properties. We found that miR-147b is a
posttranscriptional regulator of DUSP8 that is highly expressed in
patients with LUAD and is associated with lower survival. NanoString
analysis revealed that the MAPK signaling pathway is mainly affected by
overexpression of miR-147b, leading to increased proliferation and
migration and decreased apoptosis in vitro. Moreover, induction of
miR-147b promotes tumor progression in vitro and in vivo experimental
models. Knockdown of miR-147b restored DUSP8, decreased tumor
progression in vitro, and increased apoptosis via JNK phosphorylation.
These results suggest that miR-147b plays a key role in regulating MAPK
signaling in LUAD. The link between DUSP8 and miR-147b may provide novel
approaches for the treatment of lung cancer.
