Abstract
BackgroundMelanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied.MethodsRT-PCR was used to examine the expressions of lncRNA MEG3 and E-cadherin in melanoma patients and cell lines. Then, the biological functions of lncRNA MEG3 and E-cadherin were demonstrated by transfecting lncRNA MEG3-siRNA, lncRNA MEG3-overexpression, E-cadherin-siRNA and E-cadherin-overexpression plasmids in melanoma cell lines. Moreover, CCK8 assay and colony formation assay were utilized to assess the cell proliferation; Transwell assay was performed to evaluate the cell invasive ability; and tumor xenografts in nude mice were applied to test the tumor generation. Additionally, the target interactions among lncRNA MEG3, miR-21 and E-cadherin were determined by dual luciferase reporter assay. Finally, RT-PCR and WB were further conducted to verify the regulatory roles among lncRNA MEG3, miR-21 and E-cadherin.ResultsThe clinical data showed that lncRNA MEG3 and E-cadherin expressions were both declined in carcinoma tissues as compared with their para-carcinoma tissues. Moreover, lncRNA MEG3 and E-cadherin expressions in B16 cells were also higher than those in A375 and A2058 cells. Subsequently, based on the differently expressed lncRNA MEG3 and E-cadherin in these human melanoma cell lines, we chose B16, A375 and A2058 cells for the following experiments. The results demonstrated that lncRNA MEG3 could suppress the tumor growth, tumor metastasis and formation; and meanwhile E-cadherin had the same effects on tumor growth, tumor metastasis and formation. Furthermore, the analysis of Kaplan–Meier curves also confirmed that there was a positive correlation between lncRNA MEG3 and E-cadherin. Ultimately, dual luciferase assays were further used to verify that lncRNA MEG3 could directly target miR-21 which could directly target E-cadherin in turn. Additionally, the data of RT-PCR and WB revealed that knockdown of lncRNA MEG3 in B16 cells inhibited miR-21 expression and promoted E-cadherin expression, but overexpression of lncRNA MEG3 in A375 and A2058 cells presented completely opposite results.ConclusionOur findings indicated that lncRNA MEG3 might inhibit the tumor growth, tumor metastasis and formation of melanoma by modulating miR-21/E-cadherin axis.
Highlights
Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is closely related to the development of various cancers
Results lncRNA MEG3 was low expressed in melanoma tissue/cell lines and closely related to the survival rate To explore the possible role of lncRNA MEG3 in melanoma, qRT-polymerase chain reaction (PCR) was firstly conducted to compare the expression of lncRNA MEG3 in melanoma tissue with that of the adjacent tissue
The results showed that the expression of lncRNA MEG3 was lower in melanoma tissue as compared with their para-carcinoma tissues (Fig. 1a)
Summary
Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. Despite the notable improvements in treatments made in recent years, the prognosis remains poor for advanced melanoma patients, mainly due to its high mortality with intrinsic resistance to chemotherapy or radiotherapy, aggressive clinical behavior and faster metastatic potentials [6]. Early melanoma detection is the key to improving the survival and once the diagnosis is delayed, the mortality of melanoma would be rapidly elevated [7, 8] It is very difficult for dermatopathologists in clinical work to determine the histopathologic types and tumor stages of melanoma in a subset of cases [8, 9]. Better understanding of the underlying molecular mechanisms about malignant melanoma tumorigenesis and progression will be helpful to explore novel sensitive and specific biomarker or therapeutic agents
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