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.
Keywords: WNT3A; miR-6838-5p; triple-negative breast cancer.
© 2019 John Wiley & Sons, Ltd.