Publication: RHCG inhibition promotes the sensitivity of PIK3CA-mutant non-small lung cancer to PI3K inhibitor
Authors
Muqun Wang ; Yingying Pang ; Haitao Liu
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Publisher
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Universidad de Murcia, Departamento de BiologÃa Celular e HistologÃa
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DOI
https://doi.org/10.14670/HH-18-946
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info:eu-repo/semantics/article
Description
Abstract
PIK3CA, the gene encoding the catalytic
subunit of the PI3K complex, is significantly amplified
and mutated in several cancer forms, including non
small cell lung cancer (NSCLC). Although follicular
lymphoma and chronic lymphocytic leukemia have been
treated clinically with PI3K inhibitors, there are
currently no FDA-approved medications targeting PI3K
mutations in lung cancer. In this study, by TCGA
database analysis, we found that RHCG was highly
expressed in PIK3CA-mutated NSCLC and was
associated with poor prognosis. Knockdown of RHCG in
PIK3CA-mutated NSCLC inhibited cell proliferation
and promoted apoptosis, thereby sensitizing cells to
PI3K inhibitors. Mechanistically, the knockdown of
RHCG acts synergistically with PI3K inhibitors to
produce more effective inhibition of AKT and S6RP
phosphorylation downstream of PI3K. This finding
suggests a potential NSCLC target with PIK3CA
mutations.
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