Circ_0072995 Promotes Cell Carcinogenesis via Up-Regulating miR-149-5p-Mediated SHMT2 in Breast Cancer

• Published in: Cancer management and research 2020-01, Vol.12, p.11169-11181
• Main Authors: Qi, Chuang, Qin, Xianxiong, Zhou, Zuozhi, Wang, Yan, Yang, Qin, Liao, Tianzhi
• Format: Article
• Language: English
• Subjects: Apoptosis; Binding sites; Breast cancer; Cell adhesion & migration; Cell culture; Cell growth; circ_0072995; Dehydrogenases; Experiments; Glucose; Metabolism; mir-149-5p; Original Research; shmt2; Tumorigenesis; Womens health
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S272274

Circ_0072995 is a novel identified circRNA and has been identified to involve in the metastasis of breast cancer. However, the detailed function and mechanism of circ_0072995 in the biological property of breast cancer cell remain vague. The expression of circ_0072995, microRNA (miR)-149-5p and ( ) mRNA was detected using quantitative real-time polymerase chain reaction. Western blot was used to detect the protein levels of , hexokinase-2 (HK-2), lactate dehydrogenase a chain (LDHA), and glucose transporter 1 (GLUT1). Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity analysis, cell adhesion assay and transwell assay, respectively. Glucose metabolism was calculated by measuring glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. The interaction between miR-149-5p and circ_0072995 or was confirmed by dual-luciferase reporter assay. In vivo tumorigenesis was performed using the murine xenograft model. Circ_0072995 and were up-regulated in breast cancer tissues and cell lines, and knockdown of circ_0072995 or suppressed cell malignant properties and anaerobic glycolysis; importantly, overexpression attenuated the anticancer action of circ_0072995 knockdown in breast cancer. Besides, we also found circ_0072995 directly targeted miR-149-5p, thereby regulating its downstream gene by competitively binding to miR-149-5p. Additionally, xenograft analysis showed circ_0072995 silencing suppressed tumor growth via regulating and miR-149-5p in vivo. This study demonstrated that circ_0072995 promoted cell malignant phenotypes and anaerobic glycolysis in breast cancer via up-regulating through sponging miR-149-5p, indicating a promising molecular target for breast cancer treatment.