Long Non-Coding RNA TFAP2A-AS1 Inhibits Cell Proliferation and Invasion in Breast Cancer via miR-933/SMAD2.

Abstract

BACKGROUND It is well documented that long non-coding RNAs (lncRNAs) are involved in the progression of multiple human tumors by sponging microRNAs (miRNAs). However, whether lncRNA TFAP2A-AS1 plays a role in the tumorigenesis of breast cancer (BC) remains undetermined. MATERIAL AND METHODS Real-time PCR (qRT-PCR) assay was performed to detect the relative mRNA expression of TFAP2A-AS1 and miR-933. Flow cytometry analysis, CCK-8 assay, and Transwell assay were applied to detect the effects of TFAP2A-AS1 overexpression on cell cycle, apoptosis, viability, and invasion of BC cells. In vivo proliferation assay was performed to evaluate the effects of TFAP2A-AS1 overexpression on tumor growth. Bioinformatics methods, dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were used to predict and validate the interaction between TFAP2A-AS1 and miR-933, as well as SMAD2 and miR-933. Western blot assay was performed to examine the protein expression of SMAD2 in treated BC cells. RESULTS TFAP2A-AS1 expression was significantly lower in BC tissues and cell lines, and patients with high TFAP2A-AS1 expression exhibited a better prognosis than those with low TFAP2A-AS1 expression. Overexpression of TFAP2A-AS1 in BC cells caused cell cycle arrest, promoted cell apoptosis, suppressed cell ability, and attenuated cell invasion in vitro, and inhibited tumor growth in vivo. TFAP2A-AS1 was revealed to act as a miRNA sponge for miR-933 and then regulated the expression of Smad2. CONCLUSIONS Results from the present study suggest that TFAP2A-AS1 acts as a tumor suppressor in BC via the miR-933/SMAD2 axis.

• Authors: Bin Zhou, Haiyan Guo, Jinhai Tang
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 25 Pg. 1242-1253 (Feb 15 2019) ISSN: 1643-3750 [Electronic] United States
• PMID: 30768589 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• MicroRNAs
• RNA, Long Noncoding
• SMAD2 protein, human
• Smad2 Protein
• TFAP2A protein, human
• Transcription Factor AP-2

Topics

• 3' Untranslated Regions
• Adult
• Aged
• Animals
• Apoptosis (physiology)
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinogenesis
• Cell Cycle Checkpoints (physiology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Female
• Heterografts
• Humans
• MCF-7 Cells
• Male
• Mice
• Mice, Inbred BALB C
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Prognosis
• RNA, Long Noncoding (genetics, metabolism)
• Smad2 Protein (genetics, metabolism)
• Transcription Factor AP-2 (biosynthesis, genetics)