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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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgement

This work was supported by grants from the Ministry of Science and Technology (MOST103-2320-B-038-036-MY2) Taiwan, and Tungs’ Taichung MetroHarbor Hospital (TTM-TMU-103-01), Taichung, Taiwan

Disclosure

The authors declare no conflict of interest.

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Author notes

    Authors and Affiliations

    1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ROC

      Tsang-Chi Lin MD, Po-Lin Lin MS, Ming-Chih Chou MD, PhD & Chih-Yi Chen MD, PhD

    2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan ROC

      Tzu-Chin Wu MD, PhD, Ming-Chih Chou MD, PhD & Chih-Yi Chen MD, PhD

    3. Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan ROC

      Tzu-Chin Wu MD, PhD

    4. Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan ROC

      Chih-Yi Chen MD, PhD

    5. Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan ROC

      Ya-Wen Cheng PhD & Huei Lee PhD

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    1. Tsang-Chi Lin MD
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    Correspondence to Huei Lee PhD.

    Additional information

    Tsang-Chi Lin and Po-Lin Lin equally contribute to this work.

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    Lin, TC., Lin, PL., Cheng, YW. et al. 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. Ann Surg Oncol 22 (Suppl 3), 1532–1539 (2015). https://doi.org/10.1245/s10434-015-4595-z

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    • DOI: https://doi.org/10.1245/s10434-015-4595-z

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