Circ_0007031 enhances tumor progression and promotes 5-fluorouracil resistance in colorectal cancer through regulating miR-133b/ABCC5 axis.

Abstract

Colorectal cancer (CRC) remains one of the most commonly diagnosed malignancies worldwide. Circular RNAs (circRNAs) are being found to play crucial roles in human cancer, including CRC. The purpose of this study was to explore the function and mechanism of circ_0007031 on CRC progression and 5-fluorouracil (5-FU) resistance. The levels of circ_0007031, ATP-binding cassette subfamily C member 5 (ABCC5) and miR-133b were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell survival and proliferation were detected by the 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell colony formation was evaluated using a standard colony formation assay. Transwell assays were performed to determine cell migration and invasion. Targeted correlations among circ_0007031, miR-133b and ABCC5 were verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown assays. Animal experiments were performed to observe the role of circ_0007031 in vivo. Our data indicated that circ_0007031 up-regulation was associated with CRC resistance to 5-FU. Circ_0007031 knockdown repressed CRC cell proliferation, migration and invasion and enhanced 5-FU sensitivity. Circ_0007031 directly interacted with miR-133b. Moreover, circ_0007031 knockdown regulated CRC cell progression and 5-FU sensitivity by miR-133b. ABCC5 was a direct target of miR-133b, and circ_0007031 mediated ABCC5 expression via acting as a miR-133b sponge. Furthermore, miR-133b overexpression regulated CRC cell progression and sensitivity to 5-FU by down-regulating ABCC5. Additionally, circ_0007031 knockdown suppressed tumor growth in vivo. Our current work had led to the identification of circ_0007031 knockdown that repressed CRC cell malignant progression and enhanced 5-FU sensitivity via regulating ABCC5 expression by sponging miR-133b.

• Authors: Xiaowen He, Jun Ma, Mingming Zhang, Jianhua Cui, Hao Yang
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 29 Issue 4 Pg. 531-542 ( 2020) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 32865180 (Publication Type: Journal Article)

Chemical References

• ABCC5 protein, human
• Antimetabolites, Antineoplastic
• MIRN133 microRNA, human
• MicroRNAs
• Multidrug Resistance-Associated Proteins
• RNA, Circular
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Colorectal Neoplasms (drug therapy, genetics, metabolism)
• Drug Resistance, Neoplasm
• Fluorouracil (pharmacology)
• HCT116 Cells
• Humans
• Mice
• Mice, Nude
• MicroRNAs (metabolism)
• Multidrug Resistance-Associated Proteins (metabolism)
• RNA, Circular (genetics, metabolism)
• Signal Transduction
• Transfection
• Up-Regulation