Abstract
MicroRNAs (miRNAs) are a group endogenous small non-coding RNAs that inhibit protein translation through binding to specific target mRNAs. Recent studies have demonstrated that miRNAs are implicated in the development of cancer. However, the role of miR-144 in uveal melanoma metastasis remains largely unknown. MiR-144 was downregulated in both uveal melanoma cells and tissues. Transfection of miR-144 mimic into uveal melanoma cells led to a decrease in cell growth and invasion. After identification of two putative miR-144 binding sites within the 3' UTR of the human c-Met mRNA, miR-144 was proved to inhibit the luciferase activity inMUM-2B cells with a luciferase reporter construct containing the binding sites. In addition, the expression of c-Met protein was inhibited by miR-144. Furthermore, c-Met-mediated cell proliferation and invasion were inhibited by restoration of miR-144 in uveal melanoma cells. In conclusion, miR-144 acts as a tumor suppressor in uveal melanoma, through inhibiting cell proliferation and migration. miR-144 might serve as a potential therapeutic target in uveal melanoma patients.
Highlights
Uveal melanoma, including choroidal and iris melanomas, is one of the most common types of primary intraocular malignancy, with an estimated annual incidence of ~5.1 cases per million [1, 2]
The OCM-1A and MUM-2C cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM), which were supplemented with 10% fetal bovine serum (FBS) and MUM-2B, C918 in RPMI 1640 supplemented with 10% FBS
Emerging evidences have indicated that miRNAs have a crucial role in the pathogenesis of cancer through regulating genes involved in cell proliferation, migration, and invasion[15, 31,32,33]
Summary
Uveal melanoma, including choroidal and iris melanomas, is one of the most common types of primary intraocular malignancy, with an estimated annual incidence of ~5.1 cases per million [1, 2]. Major advances have been made in the diagnosis and therapy of uveal melanoma, the 5-year relative survival rate has not improved from 1973 to 2008, especially in patients with metastatic disease[7]. MiR-144 Inhibits Uveal Melanoma Cell Proliferation crucial signals that contribute to the invasive and metastatic potential of uveal melanoma might help to identify novel therapies for uveal melanoma patients. Ectopic expression of miR-144 could inhibit uveal melanoma cell proliferation and invasion in vitro. C-Met was identified as the potential targets of miR-144, and miR-144 might suppress tumor growth and invasion by repressing the expression of c-Met. Our findings suggest that miR-144 may function as a novel tumor suppressor gene in uveal melanoma and can be a potential therapy target for uveal melanoma
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