Background
Breast cancer is still a leading threat to women's lives. Long non-coding RNAs (lncRNA) associated with cancer progression are getting attention. The
Conclusion
MAFG-AS1 knockdown attenuated breast cancer progression in vitro and in vivo through activation of the JAK2/STAT3 signaling pathway by the MAFG-AS1/miR-3196/TFAP2A regulatory axis.
Methods
The expression of MAFG-AS1, microRNA-3196 (miR-3196) and transcription factor AP-2 alpha (TFAP2A) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The number of colonies was observed through colony formation assay. The protein levels of Cyclin D1, Ki67, Bcl-2 associated X protein (Bax), B-cell lymphoma2 (Bcl-2), Hexokinase II (HK2), lactate dehydrogenase A (LDHA), TFAP2A, Janus kinase 2 (JAK2), phosphorylated-JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-STAT3 were quantified by western blot. The cell apoptosis was monitored using flow cytometry. The glycolysis progression was evaluated according to glucose consumption and lactate production. The relationship between miR-3196 and MAFG-AS1 or TFAP2A was predicted by the online tool starBase and verified by the dual-luciferase reporter assay. The role of MAFG-AS1 in vivo was determined by the tumor formation assay in nude mice.
Results
MAFG-AS1 was highly expressed in tumor tissues and cells. MAFG-AS1 knockdown restrained proliferation, colony formation, and glycolysis but promoted apoptosis of breast cancer cells. MiR-3196 was a target of MAFG-AS1, and its inhibition reversed the role of MAFG-AS1 knockdown. TFAP2A was a target of miR-3196, and its overexpression abolished the effects of miR-3196 reintroduction. MAFG-AS1 knockdown suppressed the activity of the JAK2/STAT3 signaling pathway. Moreover, MAFG-AS1 knockdown reduced tumor growth in vivo.