RACK1 promotes lung cancer cell growth via an MCM7/RACK1/ Akt signaling complex.
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ABSTRACT:
SUBMITTER: Fei L
PROVIDER: S-EPMC5522230 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Project description:Approximately 90% of patients diagnosed with non-small cell lung cancer (NSCLC) die due to distant metastases. However, the complicated molecular and cellular mechanisms involved in lung cancer metastasis remain poorly understood. Copine III (CPNE3), a member of a Ca2+-dependent phospholipid-binding protein family, was identified as a novel metastasis-associated protein in NSCLC in our previous study, however, its function in metastasis remains unclear. Here, we found that CPNE3 was expressed at high levels in NSCLC tissues and advanced TNM stages and was significantly associated with poor prognosis. In addition, CPNE3 interacted with phosphorylated erb-b2 receptor tyrosine kinase 2 (pErbB2) and receptor of activated protein C kinase 1 (RACK1) and activated the focal adhesion (FA) signaling pathway in NSCLC cells. Moreover, knockdown of RACK1 inhibited cell motility in the CPNE3-overexpressed NSCLC cells. These findings offer mechanistic insights into the oncogenic roles of CPNE3 and the pivotal effects of CPNE3 as a biomarker and therapeutic target for NSCLC metastasis.
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Project description:BackgroundmiRNAs regulate a multitude of cellular processes and their aberrant regulation is linked to human cancer. However, the role of miR-425-5p in lung cancer (LCa) is still largely unclear. Here, we explored the role of miR-425-5p during LCa tumorigenesis.MethodsCell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-425-5p and PTEN.ResultsWe demonstrate that miR-425-5p is overexpressed in LCa tissue and enhances the proliferative and colony formation capacity of the LCa cell lines A549 and NCI-H1299. Through predictive binding assays, PTEN was identified as a direct gene target and its exogenous expression inhibited the pro-cancer effects of miR-425-5p. Through its ability to down-regulate PTEN, miR-425-5p activated the PI3K/AKT axis.ConclusionWe conclude that miR-425-5p promotes LCa tumorigenesis through PTEN/PI3K/AKT signaling.
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