Background: MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear. Methods: Wild-type or mutant CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan–Meier and Cox regression analysis. Results: MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors. Conclusions: MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.
ASJC Scopus subject areas
Lin, T. C., Lin, P. L., Cheng, Y. W., Wu, T. C., Chou, M. C., Chen, C. Y., & Lee, H. (2015). MicroRNA-184 Deregulated by the MicroRNA-21 Promotes Tumor Malignancy and Poor Outcomes in Non-small Cell Lung Cancer via Targeting CDC25A and c-Myc. Annals of Surgical Oncology, 22, 1532-1539. https://doi.org/10.1245/s10434-015-4595-z