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測量應用案例-20200803
閱讀：106 發(fā)布時間：2020-8-12| 提 供 商 | 美國布魯克海文儀器公司 | 資料大小 | 2.8MB |
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作者： Yan Li, Zhenhui Zhao, Wei Liu, Xun Li
Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University (Affiliated Cancer Hospital), Urumqi 830011, China
摘要：Cancer-associated fibroblasts (CAFs) are important ingredient in tumor microenviron-ment. The dynamic interplay between CAFs and cancer cells plays essential roles during tumor development and progression. However, the mechanisms of intercellular commu-nication between CAFs and cancer cells remain largely unknown. We characterized exosomes secreted from breast cancer patient-derived CAFs by transmission electron microscopy. The expression of SNHG3, miR-330-5p, and PKM (Pyruvate Kinase M1/M2) was examined by real-time QPCR and immunoblot. The function of SNHG3 on the growth and metabolism of tumor cells was used by CCK8 and mitochondrial oxygen consumption assays. The binding between SNHG3, miR-330-5p, and PKM was exam-ined by dual luciferase reporter assays. Orthotopical xenograft of breast tumor experi-ments was performed to determine the function of SNHG3 in vivo. We demonstrated that exosomes secreted from CAFs reprogram the metabolic pathways after tumor cells uptake the exosomes. CAF-secreted exosomal lncRNA SNHG3 served as a molecular sponge for miR-330-5p in breast cancer cells. Moreover, PKM could be targeted by miR-330-5p and was controlled by SNHG3 in breast cancer cells. Mechanistically, SNHG3 knock-down in CAF-secreted exosomes suppressed glycolysis metabolism and cell proliferation by the increase of miR-330-5p and decrease of PKM expression in tumor cells. SNHG3 functions as a miR-330-5p sponge to positively regulate PKM expression, inhibit mito-chondrial oxidative phosphorylation, increase glycolysis carboxylation, and enhance breast tumor cell proliferation. Overall, SNHG3 could play a major role in the develop-ment and progression of breast cancer and support the therapeutic potential of targeting communication between cancer cells and tumor microenvironment.