SNHG3 Functions as miRNA Sponge to Promote Breast Cancer Cells Growth Through the Metabolic Reprogramming

• Published in: Applied biochemistry and biotechnology Vol. 191; no. 3; pp. 1084 - 1099
• Main Authors: Li, Yan, Zhao, Zhenhui, Liu, Wei, Li, Xun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2020; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biotechnology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Carboxylation; Cell growth; Cell interactions; Cell Line, Tumor; Cell proliferation; Cell signaling; Cell Survival; Chemistry; Chemistry and Materials Science; Disease Progression; Exosomes; Exosomes - metabolism; Female; Fibroblasts; Fibroblasts - metabolism; Gene Expression Regulation, Neoplastic; Glycolysis; Humans; In vivo methods and tests; Inflammation; MCF-7 Cells; Metabolic pathways; Metabolism; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy, Electron, Transmission; miRNA; Mitochondria; Mitochondria - metabolism; Neoplasm Transplantation; Oxidative phosphorylation; Oxygen Consumption; Phosphorylation; Protein Binding; Pyruvate kinase; Pyruvate Kinase - genetics; Pyruvate Kinase - metabolism; Pyruvic acid; RNA, Long Noncoding - genetics; Transmission electron microscopy; Tumor cells; Tumors; Xenografts; Xenotransplantation; Fibroblasts; Cancer-associated; Breast cancer; Metabolism reprogram; miR-330; SNHG3
• ISSN: 0273-2289; 1559-0291
• DOI: 10.1007/s12010-020-03244-7

Cancer-associated fibroblasts (CAFs) are important ingredient in tumor microenvironment. The dynamic interplay between CAFs and cancer cells plays essential roles during tumor development and progression. However, the mechanisms of intercellular communication 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 examined by dual luciferase reporter assays. Orthotopical xenograft of breast tumor experiments 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 knockdown 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 mitochondrial oxidative phosphorylation, increase glycolysis carboxylation, and enhance breast tumor cell proliferation. Overall, SNHG3 could play a major role in the development and progression of breast cancer and support the therapeutic potential of targeting communication between cancer cells and tumor microenvironment.