Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer.
机构：[1]Department of Breast, Longhua Hospital Affiliated to Shanghai University of TCM, Shanghai, China.[2]State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.[3]Department of Breast Surgery, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China.[4]Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China.大德路总院乳腺科大德路总院乳腺科广东省中医院[5]Department of Traditional Chinese Medicine, The Ninth People's Hospital, Medical School of Shanghai Jiaotong University, Shanghai, China.
This investigation attempted to discern whether formononetin restrained progression of triple-negative breast cancer (TNBC) by blocking lncRNA AFAP1-AS1-miR-195/miR-545 axis. We prepared TNBC cell lines (i.e. MDA-MB-231 and BT-549) and normal human mammary epithelial cell line (i.e. MCF-10A) in advance, and the TNBC cell lines were, respectively, transfected by pcDNA3.1-lncRNA AFAP1-AS1, si-lncRNA AFAP1-AS1, pcDNA6.2/GW/EmGFP-miR-545 or pcDNA6.2/GW/EmGFP-miR-195. Resistance of TNBC cells in response to 5-Fu, adriamycin, paclitaxel and cisplatin was evaluated through MTT assay, while potentials of TNBC cells in proliferation, migration and invasion were assessed via CCK8 assay and Transwell assay. Consequently, silencing of lncRNA AFAP1-AS1 impaired chemo-resistance, proliferation, migration and invasion of TNBC cells (P<0.05), and over-expression of miR-195 and miR-545, which were sponged and down-regulated by lncRNA AFAP1-AS1 (P<0.05), significantly reversed the promoting effect of pcDNA3.1-lncRNA AFAP1-AS1 on proliferation, migration, invasion and chemo-resistance of TNBC cells (P<0.05). Furthermore, CDK4 and Raf-1, essential biomarkers of TNBC progression, were, respectively, subjected to target and down-regulation of miR-545 and miR-195 (P<0.05), and they were promoted by pcDNA3.1-lncRNA AFAP1-AS1 at protein and mRNA levels (P<0.05). Additionally, formononetin significantly decreased expressions of lncRNA AFAP1-AS1, CDK4 and Raf-1, while raised miR-195 and miR-545 expressions in TNBC cells (P<0.05), and exposure to it dramatically contained malignant behaviors of TNBC cells (P<0.05). In conclusion, formononetin alleviated TNBC malignancy by suppressing lncRNA AFAP1-AS1-miR-195/miR-545 axis, suggesting that molecular targets combined with traditional Chinese medicine could yield significant clinical benefits in TNBC.
基金：
National Natural Science Fund for youth (Grant No. 81704074).
第一作者机构：[1]Department of Breast, Longhua Hospital Affiliated to Shanghai University of TCM, Shanghai, China.
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通讯作者：
推荐引用方式(GB/T 7714)：
Wu Jingjing,Xu Wen,Ma Lina,et al.Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer.[J].AGING-US.2021,13(14):18191-18222.doi:10.18632/aging.203156.
APA：
Wu Jingjing,Xu Wen,Ma Lina,Sheng Jiayu,Ye Meina...&Chen Hongfeng.(2021).Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer..AGING-US,13,(14)
MLA：
Wu Jingjing,et al."Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer.".AGING-US 13..14(2021):18191-18222
医学