CircTADA2A suppresses the progression of colorectal cancer via miR-374a-3p/KLF14 axis

• Published in: Journal of experimental & clinical cancer research 2020-08, Vol.39 (1), p.160-160, Article 160
• Main Authors: Li, Zhen, Yao, Hongyu, Wang, Shihao, Li, Guobin, Gu, Xiaoming
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Apoptosis; Binding sites; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell culture; Cell cycle; Cell Movement; Cell Proliferation; circTADA2A; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Development and progression; DNA-Binding Proteins - genetics; Female; Flow cytometry; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Glucose; Glucose metabolism; Health aspects; Humans; KLF14; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Laboratory animals; Lactates; Liver cancer; Male; Metabolism; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miR-374a-3p; Neoplasm Invasiveness; Plasmids; Prognosis; Proteins; RNA, Circular - genetics; Transcription (Genetics); Transcription Factors - genetics; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-020-01642-7

Colorectal cancer (CRC) is one of the causes of cancer-related death worldwide. The aim of our study was to disclose the expression pattern and underlying molecular mechanism of circular RNA TADA2A (circTADA2A) in CRC. The levels of circTADA2A, transcriptional adaptor 2A (TADA2A), microRNA-374a-3p (miR-374a-3p) and Kruppel like factor 14 (KLF14) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Xenograft tumor assay was used to uncover the function of circTADA2A in vivo. The miRNA targets of circTADA2A were searched using circbank and starbase softwares, while DIANA TOOL was used to explore miR-374a-3p-mRNA interactions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate the target relationship of circTADA2A/miR-374a-3p/KLF14 axis. Cell cycle and apoptosis were analyzed by flow cytometry. The glycolysis of CRC cells was determined by Seahorse XF 96 Extracellular Flux Analyzer, Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II and ATP Colorimetric Assay kit. KLF14 protein level was measured by Western blot assay. CircTADA2A was abnormally down-regulated in CRC tissues and cell lines. CircTADA2A overexpression impeded CRC tumor growth in vivo. MiR-374a-3p was verified as a target of circTADA2A in CRC cells, and circTADA2A inhibited the malignant potential of CRC cells through targeting miR-374a-3p. MiR-374a-3p interacted with KLF14 messenger RNA (mRNA), and miR-374a-3p deteriorated CRC through down-regulating KLF14. CircTADA2A enhanced the abundance of KLF14 through targeting miR-374a-3p in CRC cells. CircTADA2A functioned as a tumor suppressor in CRC to inhibit the glycolysis and cell cycle and potentiate the apoptosis of CRC cells via miR-374a-3p/KLF14 axis.