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MicroRNA-196a2 Biomarker and Targetome Network Analysis in Solid Tumors

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Abstract

Introduction

MicroRNAs (miRNAs) have been linked to cancer development and progression. The molecular mechanisms underlying the genetic associations of the miRNA single nucleotide polymorphism with cancer vary by cancer site. As there are no previous studies on the miR-196a2 variant or expression in any type of cancer among our population, we aimed to determine the expression profile of mature miR-196a2 in various types of solid tumors and to analyze the impact of its polymorphism (rs11614913; C/T) on the expression levels.

Materials and Methods

The study included 230 cancer patients (including 17 types of cancer), 26 patients with pre-cancer lesions, and 100 unrelated controls. Archived formalin-fixed, paraffin-embedded specimens (n = 197) were available for both miRNA expression analysis and single nucleotide polymorphism identification. Venous blood was collected from 59 histologically confirmed sporadic cancer patients and the study controls for single nucleotide polymorphism identification. Real-time polymerase chain reaction analysis was performed for allelic discrimination and relative quantification of miR-196a2 in the study samples. In silico target gene prediction and network analysis was performed.

Results

We found that individuals with the T variant were associated with cancer risk under all genetic association models, especially in colorectal, esophageal, skin, lung, thyroid, and renal cancer. Overall and stratified analysis showed miR-196a2 over-expression in most of the current malignant tumor samples relative to their corresponding cancer-free tissues. Carriers of the C allele had significantly higher expression levels of miR-196a2. Correlation with the clinicopathological features of cancer showed organ-specific effects. Gene enrichment analysis of predicted and validated targets speculated the putative role of miR-196a2 in cancer-associated biology.

Conclusions

We highlighted cancer-type specific expression profiles of miR-196a2, which was correlated with the clinicopathological features in various types of cancer. Taken together, our results suggest that the miRNA signature could have promising diagnostic and prognostic significance.

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Acknowledgments

The authors thank the Oncology Diagnostic Unit, Suez Canal University, Egypt for providing the facilities for performing the research work at the unit and thank the patients who participated in our study.

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Authors and Affiliations

  1. Department of Histology and Cell Biology (Genetics Unit), Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Eman A. Toraih & Eman A. Mohammed

  2. Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Manal S. Fawzy

  3. Pulmonologist, Ministry of Health, Cairo, Egypt

    Mohammad H. Hussein

  4. Emergency Department, Al Jahra Hospital, Al Jahra, Kuwait

    Mohammad H. Hussein

  5. Department of Pathology, Faculty of Medicine, Port Said University, Port Said, Egypt

    Mohamad M. EL-Labban

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  1. Eman A. Toraih
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  2. Manal S. Fawzy
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  3. Eman A. Mohammed
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  4. Mohammad H. Hussein
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  5. Mohamad M. EL-Labban
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Correspondence to Manal S. Fawzy.

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Conflict of interest

Eman A. Toraih, Manal S. Fawzy, Eman A. Mohammed, Mohammad H. Hussein, and Mohamad M. El-Labban declare that they have no competing interests.

Ethical approval and informed consent

The study was conducted in accordance with the guidelines in the Declaration of Helsinki and it has been approved by the Medical Research Ethics Committee of Faculty of Medicine, Suez Canal University (Approval No. 2510).

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No sources of funding were used for this study.

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Toraih, E.A., Fawzy, M.S., Mohammed, E.A. et al. MicroRNA-196a2 Biomarker and Targetome Network Analysis in Solid Tumors. Mol Diagn Ther 20, 559–577 (2016). https://doi.org/10.1007/s40291-016-0223-2

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  • DOI: https://doi.org/10.1007/s40291-016-0223-2

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