Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. MiRNAs are recognized as important molecules in cancer biology. The aim of the study was to identify a novel biomarker miR-148b and its mechanism in the modulation of NSCLC progression.
Methods: The expressional level of miR-148b was analyzed by RT-PCR. The effect of miR-4317 on proliferation was evaluated through 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2Htetrazolium bromide (MTT) assay. The effect of miR-148b on the metastasis of NSCLC was detected through transwell assays. The verification of the target of miR-148b was assessed by TargetScan and dual-luciferase reporter assay. The related proteins in this study were analyzed by western blot.
Results: Our findings confirmed that miR-148b was decreased in NSCLC and NSCLC patients with lower expression exhibited poorer overall survival (OS). Increasing miR-148b significantly repressed proliferation, invasion and migration. More importantly, activated leukocyte cell adhesion molecule (ALCAM) was determined as the direct target of miR-148b, and reintroduction of ALCAM attenuated miR-148b effect on the progress of NSCLC. In addition, NF-κB signaling pathway was modulated by miR-148b/ALCAM axis.
Conclusions: Our results indicated that miR-148b is able to suppress NSCLC growth and metastasis via targeting ALCAM through the NF-κB pathway. These findings provided new evidence that miR-148b serves as a potential biomarker and novel target for NSCLC treatment.
Keywords: ALCAM; NF-κB; NSCLC; miR-148b; progression.
© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.