Long non-coding RNA FTH1P3 facilitates uveal melanoma cell growth and invasion through miR-224-5p.

Aamir Ahmad,Xiaoli Zheng,Yanfang Jiang,Hongwei Tang,Yamei Sun,Yonghua Liu,Xiaofeng Zhao

doi:10.1371/journal.pone.0184746

Aamir Ahmad, Xiaoli Zheng + Show 5 more

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https://doi.org/10.1371/journal.pone.0184746

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Abstract

Growing evidences indicated that Long noncoding RNAs (lncRNAs) played important roles in tumor initiation and progression. However, the function and mechnism of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) remain unknown in uveal melanoma. We showed that the expression level of FTH1P3 was upregulated in uveal melanoma cell lines and tissues. Elevated expression of FTH1P3 promoted uveal melanoma cell proliferation, cell cycle and migration. Moreover, we found that FTH1P3 was a direct target gene of miR-224-5p in uveal melanoma cell. Overexpression of FTH1P3 suppressed miR-224-5p expression and promoted the expression of Rac1 and Fizzled 5, which were the direct target genes of miR-224-5p. Furthermore, we showed that miR-224-5p expression level was downregulated in uveal melanoma cell lines and tissues. FTH1P3 expression was inversely correlated with the miR-224-5p expression in uveal melanoma tissues. Ectopic expression of miR-224-5p decreased uveal melanoma cell proliferation, cell cycle and migration. Elevated expression of FTH1P3 enhanced uveal melanoma cell proliferation and migration by inhibiting miR-224-5p expression. These results suggest that lncRNA FTH1P3 plays a crucial role in uveal melanoma. Investigation of the underlying mechanism may be a target for the treatment of uveal melanoma.

Highlights

Uveal melanoma is the most common primary intraocular malignancy cancers with a high mortality of about 50%[1,2,3,4]
ferritin heavy chain 1 pseudogene 3 (FTH1P3) expression level was overexpressed in uveal melanoma cell lines and samples
The expression level of FTH1P3 was upregulated in uveal melanoma cell lines (C918, MUM2B, OCM-1A and MUM-2C) compared to that in melanocyte cell line (D78) (Fig 1A)

Summary

Introduction

Uveal melanoma is the most common primary intraocular malignancy cancers with a high mortality of about 50%[1,2,3,4]. Metastasis is the most common cause for the high death rate of this disease[5,6,7]. No effective treatment is available for patients with metastatic disease because the biology of uveal melanoma initiation and dissemination is unknown[8,9,10]. Despite several advances in chemotherapy, radiotherapy and surgery, the five year survival rate is still unstatisfied [11,12,13,14]. It is important to study the molecular event underlying progression and to find the novel therapeutic target of uveal melanoma.

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