Liu Tan, Wang Ziming, Dong Menghao, Wei Jingjing, Pan Yueyin
Department of Oncology, Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230032, P.R. China.
Department of Oncology, The First Affiliated Hospital of The University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.
Oncol Lett. 2021 May;21(5):367. doi: 10.3892/ol.2021.12628. Epub 2021 Mar 10.
MicroRNAs (miRNAs/miRs) play key roles in cancer progression. Extensive research has revealed that miR-26a is abnormally expressed and functions as a tumor suppressor in numerous types of cancer. Thus, the present study was undertaken to investigate the regulatory role and potential mechanism of action of miR-26a in breast cancer. Furthermore, the present study aimed to examine the alterations in miR-26a expression and its effects on human breast cancer cells. Reverse transcription-quantitative PCR was conducted to assess the differences in miR-26a expression between human breast cancer and normal breast specimens. A Cell Counting Kit-8 assay and cloning experiments were used to detect cell proliferation and clone formation. Wound healing and Transwell assays were performed to examine cell migration and invasion. A luciferase activity experiment was utilized to validate the association between miR-26a and family with sequence similarity 98 member A (FAM98A). Western blotting was conducted to detect the protein expression levels of FAM98A, sonic hedgehog signaling molecule (SHH), smoothened, frizzled class receptor (SMO) and GLI family zinc finger 1 (GLI1). The results indicated that miR-26a expression was decreased in breast carcinoma tissues and cell lines. Moreover, overexpression of miR-26a significantly suppressed cell proliferation, clone formation ability and metastasis, and it sensitized breast cancer cells to docetaxel. It was demonstrated that miR-26a directly targeted FAM98A, and that FAM98A, SHH, SMO and GLI1 expression levels were decreased in cells transfected with miR-26a mimics. Collectively, the results of the present study suggested that miR-26a negatively regulated the expression of FAM98A, indicating that it may play a key role in the suppression of breast carcinogenesis.
微小RNA（miRNA/miR）在癌症进展中发挥关键作用。广泛研究表明，miR-26a在多种癌症中表达异常且发挥肿瘤抑制作用。因此，本研究旨在探讨miR-26a在乳腺癌中的调控作用及潜在作用机制。此外，本研究旨在检测miR-26a表达的变化及其对人乳腺癌细胞的影响。采用逆转录定量PCR评估人乳腺癌组织与正常乳腺标本中miR-26a表达的差异。使用细胞计数试剂盒-8检测法和克隆实验检测细胞增殖和克隆形成。进行伤口愈合实验和Transwell检测以检测细胞迁移和侵袭。利用荧光素酶活性实验验证miR-26a与序列相似性家族98成员A（FAM98A）之间的关联。采用蛋白质印迹法检测FAM98A、音猬因子信号分子（SHH）、 smoothened、卷曲蛋白家族受体（SMO）和GLI家族锌指蛋白1（GLI1）的蛋白表达水平。结果表明，miR-26a在乳腺癌组织和细胞系中的表达降低。此外，miR-26a的过表达显著抑制细胞增殖、克隆形成能力和转移，并使乳腺癌细胞对多西他赛敏感。结果表明，miR-26a直接靶向FAM98A，并且在转染miR-26a模拟物的细胞中FAM98A、SHH、SMO和GLI1的表达水平降低。总体而言，本研究结果表明miR-26a负向调节FAM98A的表达，表明其可能在抑制乳腺癌发生中起关键作用。
