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Cited by 103MicroRNA in disease regulationEsophageal Cancer Research and TreatmentCancer-related molecular mechanisms research

Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma

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Nouraee, Nazila, Van Roosbroeck, Katrien, Vasei, Mohammad, Semnani, Shahriar, Samaei, Nader Mansour, Naghshvar, Farshad, Omidi, Abbas Ali, Calin, George A. +1 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0073009PMC PMC3769386
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Abstract

OBJECTIVE: MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells. DESIGN: MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion. RESULTS: MiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4. CONCLUSIONS: MiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment.

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  • miR-21 works as a micro-environmental signaling molecule to promote invasion behavior of tumor cells.

    “Moreover, the co-culture experiment confirmed that miR-21 works as a micro-environmental signaling molecule to promote invasion behavior of tumor cells (43).”

    From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [43]

    The Results report that KYSE-30 tumor cells invaded more when co-cultured with fibroblasts or exposed to fibroblast-conditioned medium, and the Discussion calls miR-21 a microenvironment signaling molecule. But inhibiting miR-21 in fibroblasts produced a nonsignificant reduction in invasion, so the co-culture experiment does not confirm that miR-21 itself caused the increased invasion. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Upregulation of miR-21 in esophageal tumors was mainly confined to fibroblasts within the vicinity of tumor cells.

    “As we have currently reported (43), the upregulation of miR-21 in esophageal tumors was mainly confined to the fibroblasts within the vicinity of the tumor cells.”

    From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [43]

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Cited by

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Authors
Nouraee, N., Van Roosbroeck, K., Vasei, M., Semnani, S., Samaei, N. M., Naghshvar, F., Omidi, A. A., Calin, G. A., & Mowla, S. J.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Shariati Hospital (IR)
  • Golestan University of Medical Sciences (IR)
  • Mazandaran University of Medical Sciences (IR)
  • Tarbiat Modares University (IR)
Corresponding author
Mowla, Seyed Javad
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-09-10
Volume
8
Issue
9
Pages
e73009
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0073009
PMC
PMC3769386
OpenAlex
W2006978520
Cited by
103
References
2
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 14 · 2019: 8 · 2018: 9 · 2017: 15 · 2016: 14 · 2015: 7 · 2014: 11 · 2013: 1
FWCI
3.87
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Belgian American Educational Foundation
  • Yazd University
  • Koning Boudewijnstichting
  • Golestan University of Medical Sciences
  • University of Texas MD Anderson Cancer Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
miR-21, esophageal squamous cell carcinoma, cancer-associated fibroblasts, tumor microenvironment, stromal fibroblasts, cell migration, cell invasion, S100A4, tumor stroma
MeSH terms
Esophageal Squamous Cell Carcinoma, Carcinoma, Squamous Cell, Cell Movement, Esophageal Neoplasms, Fibroblasts, Humans, Immunohistochemistry, Organ Specificity, Biomarkers, Up-Regulation, Gene Expression Regulation, Neoplastic, Culture Media, Conditioned, Coculture Techniques, Tissue Inhibitor of Metalloproteinase-3, Collagen Type IV, MicroRNAs, Cell Line, Tumor, Neoplasm Grading

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