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Identification of Differentially Expressed K-Ras Transcript Variants in Patients With Leiomyoma

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Abstract

Purpose

Molecular studies have demonstrated a wide range of gene expression variations in uterine leiomyoma. The rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase (RAS/RAF/MAPK) is the crucial cellular pathway in transmitting external signals into nucleus. Deregulation of this pathway contributes to excessive cell proliferation and tumorigenesis. The present study aims to investigate the expression profile of the K-Ras transcripts in tissue samples from patients with leiomyoma.

Methods

The patients were leiomyoma cases who had no mutation in mediator complex subunit 12 (MED12) gene. A quantitative approach has been applied to determine the difference in the expression of the 2 main K-Ras messenger RNA (mRNA) variants. The comparison between gene expression levels in leiomyoma and normal myometrium group was performed using relative expression software tool.

Results

The expression of K-Ras4B gene was upregulated in leiomyoma group (P =.016), suggesting the involvement of K-Ras4B in the disease pathogenesis. Pairwise comparison of the K-Ras4B expression between each leiomyoma tissue and its matched adjacent normal myometrium revealed gene upregulation in 68% of the cases. The expression of K-Ras4A mRNA was relatively upregulated in leiomyoma group (P =.030). In addition, the mean expression of K-Ras4A gene in leiomyoma tissues relative to normal samples was 4.475 (95% confidence interval: 0.10-20.42; standard error: 0.53-12.67). In total, 58% of the cases showed more than 2-fold increase in K-Ras4A gene expression.

Conclusion

Our results demonstrated increased expression of both K-Ras mRNA splicing variants in leiomyoma tissue. However, the ultimate result of KRAS expression on leiomyoma development depends on the overall KRAS isoform balance and, consequently, on activated signaling pathways.

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Authors and Affiliations

  1. Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran

    Nooshin Zolfaghari MSc & Mehrdad Hashemi PhD

  2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Shirin Shahbazi PhD

  3. Molecular Medicine Department, Pasteur Institute of Iran, Tehran, 1316943551, Iran

    Mahnaz Torfeh MSc, Maryam Khorasani MSc & Reza Mahdian MD, PhD

Authors
  1. Nooshin Zolfaghari MSc
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  2. Shirin Shahbazi PhD
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  3. Mahnaz Torfeh MSc
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  4. Maryam Khorasani MSc
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  5. Mehrdad Hashemi PhD
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  6. Reza Mahdian MD, PhD
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Corresponding author

Correspondence to Reza Mahdian MD, PhD.

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Zolfaghari, N., Shahbazi, S., Torfeh, M. et al. Identification of Differentially Expressed K-Ras Transcript Variants in Patients With Leiomyoma. Reprod. Sci. 24, 1438–1443 (2017). https://doi.org/10.1177/1933719116689596

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