期刊
INTERNATIONAL JOURNAL OF CANCER
卷 129, 期 11, 页码 2621-2631出版社
WILEY
DOI: 10.1002/ijc.25939
关键词
microRNA; non-small cell lung cancer; brain metastasis; biomarker; migration
类别
资金
- NIH [R01CA130940, R21LM009706-01, SFAZ CAA 0244-08, SFAZ CAA 0243-08]
- Science Foundation of Arizona [SFAZ CAA 0244-08, SFAZ CAA 0243-08]
- IBIS Foundation of Arizona
- TGen Foundation
- SHC Foundation
- The Howard Hughes Medical Institute
- ASU School of Life Sciences
Brain metastasis (BM) can affect similar to 25% of nonsmall cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. microRNAs (miRNAs) regulate the expression of target mRNAs. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment, and prognosis. We investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from seven patients with BM (BM+) and six without BM (BM-). Using t-test and further qRT-PCR validation, eight miRNAs were confirmed to be significantly differentially expressed. Of these, expression of miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. This classifier was used on a validation cohort (n = 15), and it correctly classified 12/15 patients. Gene expression analysis comparing A549 parental and A549 cells stably transfected to over-express miR-328 (A549-328) identified several significantly differentially expressed genes. PRKCA was one of the genes over-expressed in A549-328 cells. Additionally, A549-328 cells had significantly increased cell migration compared to A549 cells, which was significantly reduced upon PRKCA knockdown. In summary, miR-328 has a role in conferring migratory potential to NSCLC cells working in part through PRKCA and with further corroboration in additional independent cohorts, these miRNAs may be incorporated into clinical treatment decision making to stratify NSCLC patients at higher risk for developing BM.
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