LncRNA MEG3 promotes melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis
Authors: Lifei Zhu
Xi Lin
Chaoying Yang
Yanchang Li
Zhixin Zheng
Liangcai Wu
Journal: Cancer Cell International (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Development and progression of tumor; Melanoma; lncRNA MEG3/miR-21/E-cadherin regulatory axis.
Affiliations: 1Department of Dermatology, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26, Yuancun ErHeng Road, Guangzhou, 510655 China., 2Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632 China.

Abstract:  Background: 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. However, the role of lncRNA MEG3 in melanoma has seldom been studied. Methods: RT-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. Results: The 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. Conclusion: Our findings indicated that lncRNA MEG3 might inhibit the tumor growth, tumor metastasis and formation of melanoma by modulating miR-21/E-cadherin axis. 

Retracted: No

PubPeer comments:
 This paper has a Correction for a puzzling error:  *Following publication of the original article [1], we were notified of a mistake in the articleu2019s title. The title should read u201cinhibitsu201d instead of u201cpromotesu201d, as follows: u201cLncRNA MEG3 inhibits melanoma growth, metastasis and formation through modulating miR-21 E-cadherin axisu201d. * Could the authors also please check Figure 5C? * Red boxes: The A2058 panel looks similar to the A375 panel * Blue boxes: The A2058-E-cadherin panel looks similar to the A375-E-cadherin panel  , 
 Could the authors also comment on why this description of the results in the abstract is not supported by the results in the paper. Specifically, this sentence from the abstract:  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 . Figure 7 shows opposite results for miR-21 expression following MEG3 knockdown in B16 cells and there are no results presented on E-Cadherin expression following MEG3 knockdown in the cell lines. In addition, the effect of MEG3 overexpression (without added miR-21) on E-Cadherin expression is not shown. Data on E-Cadherin expression after the knockdown and overexpression of MEG3 would of course be very interesting and relevant to include. ,