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Authors Shi G, Li H, Gao F, Tan Q
Received 18 December 2017
Accepted for publication 26 April 2018
Published 20 June 2018 Volume 2018:11 Pages 3583—3595
DOI https://doi.org/10.2147/OTT.S160143
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 4
Editor who approved publication: Dr William Cho
Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients
with advanced disease is relatively poor. Recent studies indicate that long
non-coding RNAs are involved in the pathogenesis of malignant melanoma. This
study aims to investigate the role of the long non-coding RNA H19 in melanoma
and to explore the underlying molecular mechanisms.
Materials and
methods: The expression levels of H19 in
clinical samples and melanoma cells were determined by quantitative real-time
PCR. The cell growth and cell metastasis were assessed by Cell Counting Kit 8,
cell invasion and wound healing assays. Cell apoptosis and cell cycle were
determined by flow cytometry. Protein levels were determined by Western
blotting assay.
Results: H19 was highly expressed in melanoma tissues compared to normal
adjacent skin tissues, and the tissue expression level of H19 from melanoma
patients with metastasis was significantly higher than that from patients
without distant metastasis. In addition, the high expression of H19 in melanoma
tissues was associated with advanced tumor invasion and TNM stage, distal
metastasis, lymph node metastasis and shorter overall survival in patients with
melanoma. The in vitro functional assays showed that knockdown of H19 inhibited
cell growth, invasion and migration and also induced cell apoptosis as well as
G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and
Western blot experiments showed that knockdown of H19 differentially regulated
the epithelial–mesenchymal transition (EMT)-related gene expressions and
reversed EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor
growth and modulated the expressions of EMT-related genes in nude mice.
Conclusion: The results from this study suggest that upregulation of H19
contributes to melanoma development and progression.
Keywords: melanoma, lncRNAs, H19, apoptosis, invasion and migration,
epithelial–mesenchymal transition