Department 1 of Breast Surgery, Linyi Cancer Hospital, Linyi, Shandong, China.
Department of Oncological Radiotherapy, Wenzhou Central Hospital, Zhejiang Province, China.
J Gene Med. 2019 Dec;21(12):e3129. doi: 10.1002/jgm.3129. Epub 2019 Dec 3.
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.
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.
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.
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.
三阴性乳腺癌（TNBC）已成为危害女性身心健康的常见肿瘤，其特点是复发相对较快，脑转移发生率较高。研究越来越表明，microRNAs 在 TNBC 的进展中发挥关键作用。然而，miR-6838-5p 在 TNBC 中的功能尚未报道，需要进一步探索。
在本研究中，我们通过定量逆转录-聚合酶链反应发现了 TNBC 细胞中 miR-6838-5p 的表达。通过 Transwell 和 Western blot 测定，研究了上调或下调 miR-6838-5p 对 TNBC 侵袭性、Wnt 途径激活和上皮-间充质转化（EMT）的影响。利用荧光素酶报告、Western blot 和 RIP 测定揭示了 miR-6838-5p 在 TNBC 中的作用机制。挽救实验通过 Wnt 途径证明了 miR-6838-5p/WNT3A 网络在 TNBC 侵袭性中的作用。
在 TNBC 细胞中发现表达下调的 miR-6838-5p。上调 miR-6838-5p 抑制了 TNBC 细胞的侵袭、迁移和 Wnt 途径的阻断。然而，下调 miR-6838-5p 则导致相反的结果。此外，通过荧光素酶报告、Western blot 和 RIP 测定，我们发现 miR-6838-5p 可以与 WNT3A 结合并负调控 WNT3A 的表达。通过挽救实验，我们证明了 WNT3A 的过表达部分挽救了 miR-6838-5p 过表达介导的抑制作用，而 WNT3A 的敲低部分挽救了 miR-6838-5p 抑制对 TNBC 进展的促进作用。
综上所述，本研究结果表明，miR-6838-5p 通过靶向 WNT3A 抑制 Wnt 途径抑制细胞增殖、转移和 EMT 过程，可能为 TNBC 的治疗策略提供新的思路。
