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MiR-148b suppressed non-small cell lung cancer progression via inhibiting ALCAM through the NF-κB signaling pathway.

Thorac Cancer. 2020 Feb;11(2):415-425. doi:10.1111/1759-7714.13285. Epub 2019 Dec 27
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摘要


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.

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