MicroRNA-645 targets urokinase plasminogen activator and decreases the invasive growth of MDA-MB-231 triple-negative breast cancer cells

Abstract

BackgroundUrokinase plasminogen activator (uPA) promotes the in vivo invasive growth of HCC cells by cleaving and activating matrix metalloproteinases (MMPs) to induce the destruction of the extracellular matrix of triple-negative breast cancer (TNBC) cells. The identification of microRNAs that target uPA and decrease uPA expression would be useful for attenuating the in vivo invasive growth of TNBC cells.Materials and methodsMicroRNA-645 (miR-645) was identified using an online tool (miRDB) as potentially targeting uPA; miR-645 inhibition of uPA was confirmed by western blot experiments. The effects of miR-645 on the in vivo invasive growth of TNBC cells were examined using an intrahepatic tumor model in nude mice, and the miR-645 mechanism of action was explored with MMP cleaving experiments.ResultsThrough virtual screening, we discovered that miR-645 potentially targeted the uPA 3′ untranslated region. This targeting was confirmed by western blot experiments and miR-645 lentiviral particle (LV-645) transduction that inhibited uPA expression in MDA-MB-231 TNBC cells. The LV-645 inhibition of uPA led to the decreased invasive growth of TNBC cells in nude mice. The mechanism data indicated that the uPA inhibition resulted in a decreased cleaving of the pro-MMP-9 protein.ConclusionTargeting uPA with miR-645 decreased the in vivo invasive growth of TNBC cells. These results suggest that miR-645 may represent a promising treatment strategy for TNBC.

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

“…Hepatic portal vein injection was used to inoculate HCC cells into the liver of nude mice, simulating the recurrence or metastasis of HCC cells in patients. In addition Meng et al [70][71][72] established a research model for the invasion of malignant tumor cells in the liver of nude mice. Li et al 73 developed a breast cancer lung metastasis model in nude mice.…”

Effects of VEGFR1+ hematopoietic progenitor cells on pre-metastatic niche formation and in vivo metastasis of breast cancer cells

“…For different experiments, cells were treated with inhibitors of various pathways. Then, cells were mixed with biological–medical gel (Cai-Hong-Yi-Xue-She-Bei Corporation, Kunming City, Yunnan Province, China) and adhered to the surface of the nude mice’s livers (Meng et al 2018 ). After 4–8 weeks of growth, mice were screening by Micro PET experiments following methods described by Feng et al ( 2018 ), Xie et al ( 2018 ), and Zhang et al ( 2018a ).…”

“…After 4–8 weeks of growth, mice were screening by Micro PET experiments following methods described by Feng et al ( 2018 ), Xie et al ( 2018 ), and Zhang et al ( 2018a ). Livers showing nodules formed by the MDA-MB-231 cells were collected for Masson staining, following methods described in our previous work (Meng et al 2018 ). Photographs of the Masson staining were quantitatively analyzed to determine the relative invasive growth of the MDA-MB-435s-HM cells using ImageJ software, following methods described in our previous work (Meng et al 2018 ): the thicknesses of the nodules or liver were determined, and the relative invasive growth of the MDA-MB-231 cells in the nude mouse liver (the nodule thickness relative to that of the liver organ) was calculated as follows: (nodule thickness in the control group)/(liver thickness in the control group) × 100% or (nodule thickness in the experimental group)/(liver thickness in the experimental group) × 100%.…”

“…Livers showing nodules formed by the MDA-MB-231 cells were collected for Masson staining, following methods described in our previous work (Meng et al 2018 ). Photographs of the Masson staining were quantitatively analyzed to determine the relative invasive growth of the MDA-MB-435s-HM cells using ImageJ software, following methods described in our previous work (Meng et al 2018 ): the thicknesses of the nodules or liver were determined, and the relative invasive growth of the MDA-MB-231 cells in the nude mouse liver (the nodule thickness relative to that of the liver organ) was calculated as follows: (nodule thickness in the control group)/(liver thickness in the control group) × 100% or (nodule thickness in the experimental group)/(liver thickness in the experimental group) × 100%. The inhibition rate for each group was calculated as follows: [(relative invasive growth in the control group) − (relative invasive growth in the experimental group)]/(relative invasive growth in the control group) × 100%.…”

<p>miR-596 suppresses the expression of Survivin and enhances the sensitivity of osteosarcoma cells to the molecular targeting agent anlotinib</p>

“…31 Images of the results from MicroPET or H&E staining were quantitatively analyzed via Image J software, according to previously detailed methods. 32,33 The inhibition rate of each group was calculated following the methods provided by Wei et al (2019). 34…”