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Published on: January 7, 2019
miR-147b mediated suppression of DUSP8 promotes lung cancer progression
Kati Turkowski1,2, Frederik Herzberg1, Stefan Günther1
1Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), Bad Nauheim, 61231, Germany.
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.
Insights
MicroRNA-147b (miR-147b) silences Dual-specificity phosphatase 8 (DUSP8) in lung adenocarcinoma, promoting tumor growth. Restoring DUSP8 via miR-147b inhibition offers potential lung cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Dual-specificity phosphatase 8 (DUSP8) is a selective c-Jun N-terminal kinase (JNK) phosphatase within the mitogen-activated protein kinase (MAPK) signaling pathway.
- Dysregulation of MAPK signaling is implicated in various cancers, including lung adenocarcinoma (LUAD).
Purpose of the Study:
- To investigate the role of miR-147b in regulating DUSP8 expression and its impact on lung adenocarcinoma progression.
- To explore the therapeutic potential of targeting the miR-147b/DUSP8 axis in LUAD.
Main Methods:
- Utilized cell culture and in vivo models to study DUSP8 and miR-147b interactions.
- Employed siRNA for DUSP8 silencing and NanoString analysis to assess MAPK pathway activity.
- Correlated miR-147b and DUSP8 expression levels with patient survival data.
Main Results:
- miR-147b was found to be overexpressed in LUAD, silencing DUSP8 and correlating with poor patient survival.
- DUSP8 overexpression exhibited tumor-suppressive effects, while its silencing promoted LUAD progression.
- miR-147b induction enhanced proliferation, migration, and tumor progression, while its knockdown restored DUSP8, inhibited tumor growth, and increased apoptosis via JNK phosphorylation.
Conclusions:
- miR-147b acts as a key posttranscriptional regulator of DUSP8 in LUAD, driving tumor progression through MAPK signaling.
- The miR-147b/DUSP8 regulatory axis represents a promising therapeutic target for lung adenocarcinoma treatment.
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