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A novel signaling role for miR-451 in esophageal tumor microenvironment and its contribution to tumor progression

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Abstract

Objective

We evaluated miR-451 expression in serum and tissue samples of esophageal squamous cell carcinoma (ESCC) patients. Then, we examined a secretory role of miR-451 in esophageal tumor microenvironment.

Methods

miR-451 expression was evaluated in 39 serum samples from esophageal SCC patients compared to 39 normal individuals as well as 26 pairs of fresh-frozen tumor and adjacent normal tissues from patients with ESCC, using qRT-PCR. In a co-culture system of human normal fibroblasts (HFSF-PI3) and esophageal cancer cell line (KYSE-30), we evaluated exosomal miR-451 secretion into the conditioned medium (CM) of both cell lines. Then, we analyzed the effect of primiR-451-transfected fibroblasts on the migration potency of their neighboring KYSE-30 cells.

Results

We detected miR-451 over-expression in serum samples of esophageal cancer patients compared to the normal group (P = 0.005). Interestingly, fresh-frozen tumor tissues from the same patients showed miR-451 down-regulation compared to their adjacent normal counterparts (P = 0.043). Co-culturing the KYSE-30 cell line with normal fibroblasts significantly induced miR-451 exosomal secretion into the CM. Moreover, co-culture of KYSE-30 cell line with miR-451-over-expressing fibroblasts significantly induced migration tendency in KYSE-30 cell line compared to the mock-transfected fibroblasts (P < 0.0001). In this system, MIF expression (a validated target of miR-451) in the KYSE-30 cell line was increased although this alteration was not statistically significant (fold change = 4.44).

Conclusions

Our data suggest that cancer-associated fibroblasts use exosomal miR-451 as a signaling molecule to provide a favorable niche for tumor cell migration and cancer progression. Our findings provide new insights into the stromal role of miR-451 in the esophageal tumor microenvironment as a communicatory molecule and suggest a signaling role for miR-451 in extracellular matrix cross-talks.

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Acknowledgements

We are thankful to Dr. Mohammad Vasei and Dr. Mohsen Sharifi for their kind help and advices. This work was financially supported by research grants from research deputies of research deputy of Iran Ministry of Science, Research and Technology and Golestan University of Medical Sciences.

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Authors and Affiliations

  1. Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran

    S. Khazaei

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

    N. Nouraee & S. J. Mowla

  3. Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran

    A. Moradi

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  1. S. Khazaei
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  2. N. Nouraee
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  3. A. Moradi
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  4. S. J. Mowla
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Correspondence to S. J. Mowla.

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All clinical sampling conducted in accordance with ethical principles and patients satisfaction.

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Khazaei, S., Nouraee, N., Moradi, A. et al. A novel signaling role for miR-451 in esophageal tumor microenvironment and its contribution to tumor progression. Clin Transl Oncol 19, 633–640 (2017). https://doi.org/10.1007/s12094-016-1575-0

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  • DOI: https://doi.org/10.1007/s12094-016-1575-0

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