CIAPIN1 Targeted NHE1 and ERK12 to Suppress NSCLC Cells’ Metastasis and Predicted Good Prognosis in NSCLC Patients Receiving Pulmonectomy

Abstract EN

Objective.

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) acts as a downstream effector of the receptor tyrosine kinase-Ras signaling pathway and has been reported as a candidate tumor suppressor gene in various cancers.

Our current study was aimed at investigating the prognostic impact of CIAPIN1 on Non-Small-Cell Lung Carcinoma (NSCLC) patients and the effect of CIAPIN1 on NSCLC A549 cells’ metastasis.

Methods.

Western blot analysis was applied to detect CIAPIN1 expression; Kaplan-Meier survival analysis was used to evaluate the effect of CIAPIN1 on NSCLC patients’ prognosis.

Wound healing assay, Transwell chamber invasion analysis, and tumorigenicity assay in BALB/c nude mice were used to measure the metastasis potential of A549 cells.

Results.

We found that CIAPIN1 overexpression indicated good survival duration during the follow-up period.

CIAPIN1 overexpression inhibited the migration, invasion, MMPs, and EMT-associated markers in A549 cells.

Further, NHE1 (Na+/H+ exchanger 1) expression and ERK1/2 phosphorylation decreased along with CIAPIN1 upregulation.

Importantly, treating A549 cells with CIAPIN1 overexpression with the NHE1-specific inhibitor, Cariporide, further inhibited the metastatic capacity, MMP expression, EMT-associated markers, and phosphorylated ERK1/2.

Treatment with the MEK1-specific inhibitor, PD98059, induced nearly the same suppression of CIAPIN1 overexpression-dependent metastatic capacity, MMP expression, and EMT-associated markers as was observed with Cariporide.

Further, Cariporide and PD98059 exert synergistical suppression of A549 cells’ metastatic capacity.

Conclusion.

Thus, the current results implied a potential management by which CIAPIN1 upregulation may have a crucial effect on the suppression of NSCLC, indicating that overexpression of CIAPIN1 might serve as a combination with chemotherapeutical agents in NSCLC therapy.