Background: Calbindin 1 (CALB1), a constituent Ca²⁺-binding protein, has been reported to prevent apoptotic death in tumor cells. However, the microRNA-mediated regulatory mechanism of CALB1 expression in nonsmall cell lung cancer (NSCLC) has not been reported so far.

Methods and Results: In this study, CALB1 was found to be overexpressed in NSCLC tissues through the immunohistochemistry assay. Higher CALB1 expression levels were significantly associated with the tumor–node–metastasis (TNM) stage. Moreover, higher expression of CALB1 predicts poor survival in NSCLC patients using the Kaplan–Meier plotter online analysis. In addition, miR-454-3p was predicted to target CALB1 using a software algorithm, validated by the luciferase assay, and analyzed by quantitative polymerase chain reaction and Western blot. The authors further found that miR-454-3p was downregulated in NSCLC tissues and cell lines. Downregulation of CALB1 or upregulation of miR-454-3p significantly suppressed NSCLC cell proliferation and induced cell apoptosis as shown by CCK-8 and flow cytometry analysis, respectively.

Conclusions: Our results suggest that CALB1 is a direct target of miR-454-3p and downregulation of CALB1 by miR-454-3p suppressed NSCLC cell functions, which may shed light on its potential application in NSCLC therapy.