Lei Du1, Xingguang Tao2, Xiaowei Shen3. 1. General Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. 2. Department of Orthopedics, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, Shanghai, 201700, China. 3. Department of General Surgery, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, No.1158, Gong Yuan Dong Road , Shanghai, 201700, China. damonsxw@outlook.com.
Abstract
BACKGROUND: Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exos) exhibit various roles in breast cancer development. The molecular mechanisms underlying hucMSC-exos in breast cancer cells are not fully clear. In the current study, we set out to investigate the downstream signaling pathways of hucMSC-exos in MCF-7 cells, a commonly used cell line to study breast cancer. METHODS: hucMSC-exos' effects on MCF-7 cells were examined using immunocytochemistry. An inhibitor and a mimic of miR-21-5p were administered. The mRNA and protein levels of ZNF367 were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR)and western blotting. Transwell assays were used to measure invasion and migration. Dual-luciferase assays were performed to investigate the binding sites between miR-21-5p and ZNF367. To manipulate expression, an overexpressing of ZNF367 approach was utilized. RESULTS: We confirmed that hucMSC-exos can be internalized by MCF-7 cells. hucMSC-exos dramatically inhibited migration and invasion behaviors through downregulation of ZNF367 and upregulation of miR-21-5p. miR-21-5p directly binds on 3'UTR of ZNF367. miR-21-5p mimic partially abolished overexpressed ZNF367-induced migration and invasion. In breast cancer tissues, there was a negative correlation between miR-21-5p and ZNF367 levels. The similar results were also obtained in human breast cancer MDA-MB-231 cells. CONCLUSION: husMSC-exos are anti-oncogenic in MCS-7 cells. husMSC-exos suppress ZNF367 expression and promote miR-21-5p expression. miR-21-5p opposes ZNF367's actions during breast cancer development. miR-21-5p direct binds ZNF367 3'UTR to inhibit ZNF367 expression. The interaction between miR-21-5p and ZNF367 may serve as a future therapeutic approach to improve breast cancer prognosis.
BACKGROUND: Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exos) exhibit various roles in breast cancer development. The molecular mechanisms underlying hucMSC-exos in breast cancer cells are not fully clear. In the current study, we set out to investigate the downstream signaling pathways of hucMSC-exos in MCF-7 cells, a commonly used cell line to study breast cancer. METHODS: hucMSC-exos' effects on MCF-7 cells were examined using immunocytochemistry. An inhibitor and a mimic of miR-21-5p were administered. The mRNA and protein levels of ZNF367 were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR)and western blotting. Transwell assays were used to measure invasion and migration. Dual-luciferase assays were performed to investigate the binding sites between miR-21-5p and ZNF367. To manipulate expression, an overexpressing of ZNF367 approach was utilized. RESULTS: We confirmed that hucMSC-exos can be internalized by MCF-7 cells. hucMSC-exos dramatically inhibited migration and invasion behaviors through downregulation of ZNF367 and upregulation of miR-21-5p. miR-21-5p directly binds on 3'UTR of ZNF367. miR-21-5p mimic partially abolished overexpressed ZNF367-induced migration and invasion. In breast cancer tissues, there was a negative correlation between miR-21-5p and ZNF367 levels. The similar results were also obtained in human breast cancer MDA-MB-231 cells. CONCLUSION: husMSC-exos are anti-oncogenic in MCS-7 cells. husMSC-exos suppress ZNF367 expression and promote miR-21-5p expression. miR-21-5p opposes ZNF367's actions during breast cancer development. miR-21-5p direct binds ZNF367 3'UTR to inhibit ZNF367 expression. The interaction between miR-21-5p and ZNF367 may serve as a future therapeutic approach to improve breast cancer prognosis.
Authors: Junfeng Li; Hirotake Komatsu; Erasmus K Poku; Tove Olafsen; Kelly X Huang; Lina A Huang; Junie Chea; Nicole Bowles; Betty Chang; Jeffrey Rawson; Jiangling Peng; Anna M Wu; John E Shively; Fouad R Kandeel Journal: Pharmaceuticals (Basel) Date: 2022-05-12
Authors: Ma'mon M Hatmal; Mohammad A I Al-Hatamleh; Amin N Olaimat; Walhan Alshaer; Hanan Hasan; Khaled A Albakri; Enas Alkhafaji; Nada N Issa; Murad A Al-Holy; Salim M Abderrahman; Atiyeh M Abdallah; Rohimah Mohamud Journal: Biomedicines Date: 2022-05-24