Serum MicroRNA‐150 Predicts Prognosis for Early‐Stage Non‐Small Cell Lung Cancer and Promotes Tumor Cell Proliferation by Targeting Tumor Suppressor Gene SRCIN1

This integrative multistage study was aimed to identify circulating microRNAs (miRNAs) as prognostic biomarkers and investigate the treatment target for early‐stage non‐small cell lung cancer (NSCLC) patients. In stage I–II NSCLC patients, we screened and validated the miRNA ratio signatures predict...

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Published in:Clinical pharmacology and therapeutics 2018-06, Vol.103 (6), p.1061-1073
Main Authors: Zhang, Liren, Lin, Jing, Ye, Yuanqing, Oba, Taro, Gentile, Emanuela, Lian, Jie, Wang, Jing, Zhao, Yang, Gu, Jian, Wistuba, Ignacio I., Roth, Jack A., Ji, Lin, Wu, Xifeng
Format: Article
Language:English
Subjects:
3' Untranslated Regions - physiology
Adaptor Proteins, Vesicular Transport - metabolism
Aged
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - mortality
Cell Movement - genetics
Cell Proliferation - genetics
Female
Genes, Tumor Suppressor - physiology
Humans
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Male
MicroRNAs - genetics
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Survival Analysis
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Summary:This integrative multistage study was aimed to identify circulating microRNAs (miRNAs) as prognostic biomarkers and investigate the treatment target for early‐stage non‐small cell lung cancer (NSCLC) patients. In stage I–II NSCLC patients, we screened and validated the miRNA ratio signatures predictive of prognosis in serum. In tumor, we found that the expression of miR‐150 in identified miRNA signatures was also associated with survival. Increased miR‐150 expression promoted NSCLC cell proliferation and migration and vice versa. Specific mRNA cleavage sites targeted by endogenous miR‐150 in 3′ untranslated region (UTR) of SRCIN1 was identified by utilizing our recently developed novel Stem‐Loop‐Array reverse‐transcription polymerase chain reaction (SLA‐RT‐PCR) assay. The blocking action of miR‐150 resulted in repressed NSCLC cell growth in vitro and knockdown of miR‐150 caused substantial tumor volume reduction in vivo. Our findings suggest that miR‐150 binding on specific recognition sites in 3′ UTR of tumor suppressor gene SRCIN1 present a potential therapeutic target for NSCLC.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.870