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Long Non-Coding RNA FTH1P3 Facilitates Uveal Melanoma Cell Growth and Invasion Through miR-224-5p

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Long Non-Coding RNA FTH1P3 Facilitates Uveal Melanoma Cell Growth and Invasion Through miR-224-5p

Xiaoli Zheng et al. PLoS One.

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. FTH1P3 expression level was overexpressed in uveal melanoma cell lines and samples.
(A) The FTH1P3 expression in the uveal melanoma cell lines (C918, MUM-2B, OCM-1A and MUM-2C) and melanocyte cell line (D78) was detected by using qRT-PCR. U6 was used as the control. (B) The FTH1P3 expression in the uveal melanoma samples and no-tumor samples was measured by using qRT-PCR. **p<0.01.
Fig 2
Fig 2. Elevated expression of FTH1P3 increased the uveal melanoma cell proliferation and migration.
(A) The expression of FTH1P3 in the uveal melanoma cell line MUM-2B treated with pcDNA-FTH1P3 was detected with qRT-PCR. (B) The cell proliferation was meaured by CCK-8 assay. Ectopic expression of FTH1P3 promoted the MUM-2B cell proliferation. (C) Elevated expression of FTH1P3 increased the MUM-2B cell cycle. (D) Wound healing assay was performed to determine the cell migration. (E) The relative ratio of wound closure per field was shown. *p<0.05, **p<0.01 and ***p<0.001.
Fig 3
Fig 3. FTH1P3 was a direct target gene of miR-224-5p.
(A) MiRDB (http://mirdb.org/cgi-bin/custom.cgi) was used to search the target gene of miR-224-5p. FTH1P3 may be a target gene of miR-224-5p. (B) The expression of miR-224-5p was measured by qRT-PCR. (C) Overexpression of miR-224-5p decreased the luciferase activity of FTH1P3-WT, but it has not decreased the luciferase activity of FTH1P3-Mut. (D) Overexpression of miR-224-5p decreased the FTH1P3 expression in the MUM-2B cell.
Fig 4
Fig 4. Overexpression of FTH1P3 decreased the miR-224-5p expression.
(A) Elevated expression of FTH1P3 decreased the miR-224-5p expression in the MUM-2B cell. (B) FTH1P3 overexpression promoted the expression of Rac1. (C) Overexpression of FTH1P3 enhanced the Fizzled 5 expression. (D) The protein expression of Rac1 was measured by western blot. FTH1P3 overexpression promoted the protein expression of Rac1. (E) The protein expression of Fizzled 5 was measured by western blot.
Fig 5
Fig 5. miR-224-5p expression level was downregulated in uveal melanoma cell lines and samples and inversely correlated with FTH1P3.
(A) The expression level of miR-224-5p in the uveal melanoma cell lines (C918, MUM-2B, OCM-1A and MUM-2C) and melanocyte cell line (D78) was determined by qRT-PCR. (B) The miR-224-5p expression was lower in the uveal melanoma samples than in the no-tumor samples. (C) The expression of miR-224-5p in the uveal melanoma tissues was inversely correlated with FTH1P3 expression. ***p<0.001.
Fig 6
Fig 6. FTH1P3 enhanced the uveal melanoma cell proliferation and migration by inhibiting the miR-224-5p expression.
(A) Ectopic expression of miR-224-5p suppressed the MUM-2B cell proliferation. (B) Overexpression of miR-224-5p suppressed the MUM-2B cell cycle. (C) Ectopic expression of miR-224-5p decreased the MUM-2B cell migration and the relative ratio of wound closure per field was shown in the right. (D) We restored miR-224-5p expression through transfecting miR-224-5p mimic into the FTH1P3 overexpressing-MUM-2B cells. The advantageous role of FTH1P3 on the MUM-2B cell proliferation was reversed by miR-224-5p overexpression. (E) Overexpression of miR-224-5p decreased the cell cycle in the FTH1P3 overexpressing-MUM-2B cell. (F) Ectopic expression of miR-224-5p suppressed the cell migration in the FTH1P3 overexpressing-MUM-2B cell. The relative ratio of wound closure per field was shown in the right. *p<0.05, **p<0.01 and ***p<0.001.

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Grant support

This study was supported by Jilin Province Science and Technology Agency (No.20160101037JC and 20170622009JC). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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