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MiR‐6838‐5p suppresses cell metastasis and the EMT process in triple‐negative breast cancer by targeting WNT3A to inhibit the Wnt pathway
Author(s) -
Liu Guozhu,
Wang Ping,
Zhang Hao
Publication year - 2019
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3129
Subject(s) - wnt signaling pathway , triple negative breast cancer , gene knockdown , cancer research , epithelial–mesenchymal transition , wnt3a , microrna , western blot , metastasis , cell migration , biology , breast cancer , signal transduction , cell , chemistry , cancer , cell culture , microbiology and biotechnology , gene , genetics , biochemistry
Background Triple‐negative breast cancer (TNBC) has become a common tumor that harms women's physical and mental health, as characterized by a relatively rapid recurrence and a high incidence of brain metastasis. Research increasingly suggests that microRNAs play key roles in the progress of TNBC. However, the function of miR‐6838‐5p in TNBC has not yet been reported, and requires additional exploration. Methods In the present study, we uncovered miR‐6838‐5p expression in TNBC cells via a quantitative reverse transcriptase‐polymerase chain reaction. Functionally, the impacts of up‐regulated or down‐regulated miR‐6838‐5p on TNBC invasiveness, Wnt pathway activation and epithelial–mesenchymal transition (EMT) were investigated via transwell and western blot assays. Mechanical analyses were utilized to unmask the miR‐6838‐5p mechanism in TNBC, including luciferase reporter, western blot and RIP assays. Rescue assays manifested the miR‐6838‐5p/WNT3A network in TNBC invasiveness through the Wnt pathway. Results Under‐expressed miR‐6838‐5p was found in TNBC cells. Up‐regulation of miR‐6838‐5p suppressed TNBC cell invasion, migration and blockade of the Wnt pathway. However, down‐regulation of miR‐6838‐5p led to opposite results. Furthermore, we found, via luciferase reporter, western blot and RIP assays, that miR‐6838‐5p could bind with WNT3A and negatively regulate WNT3A expression. Through rescue experiments, we demonstrated that the overexpression of WNT3A partially rescued the miR‐6838‐5p overexpression‐mediated inhibitory effect, and knockdown of WNT3A partially rescued the miR‐6838‐5p suppression‐mediated promotive effect on the progression of TNBC. Conclusions In summary, the results of the present study indicate that miR‐6838‐5p suppresses cell proliferation, metastasis and the EMT process in TNBC by targeting WNT3A to inhibit the Wnt pathway, which may provide a new insight into the therapeutic strategies of TNBC.