Golestan University of Medical Sciences Repository

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

Khazaei, S. and Nouraee, N. and Moradi, A. and Mowla, S.J. (2017) A novel signaling role for miR-451 in esophageal tumor microenvironment and its contribution to tumor progression. Clinical and Translational Oncology, 19 (5). pp. 633-640.

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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. © 2016, Federación de Sociedades Españolas de Oncología (FESEO).

Item Type: Article
Additional Information: cited By 0
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Depositing User: GOUMS
Date Deposited: 18 Jun 2017 15:21
Last Modified: 18 Jun 2017 15:21
URI: http://eprints.goums.ac.ir/id/eprint/5067

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