Publication: Circular RNA circ-CD44 regulates chemotherapy resistance by targeting the miR-330-5p/ABCC1 axis in colorectal cancer cells
Authors
Zhao, Shuai ; Xu, Fei ; Ji, Yiding ; Wang, Yuanyuan ; Wei, Ming ; Zhang, Like
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-516
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info:eu-repo/semantics/article
Description
Abstract
. Background. Colorectal cancer (CRC) is a
common malignant tumor worldwide, ranking fourth for
incidence. Recently, circular RNAs (circRNAs) have
been demonstrated to play a key role in chemotherapy
resistance to CRC treatment. Therefore, the role of circCD44 is investigated in CRC.
Methods. The expression levels of circ-CD44, miR330-5p, and ATP binding cassette subfamily C member 1
(ABCC1) were quantified by real-time quantitative
polymerase chain reaction (RT-qPCR) assay. The
sensitivity of CRC cells to oxaliplatin (OXA) was
assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl2H-tetrazol-3-ium bromide (MTT) assay. Colonyforming experiment was performed to measure the
colony-forming ability of CRC cells. The apoptosis,
migration, and invasion of CRC cells were determined
by flow cytometry and transwell assays. A xenograft
experiment was established to clarify the functional role
of circ-CD44 silencing in vivo. The interactional
relationship among circ-CD44, miR-330-5p, and
ABCC1 was confirmed by dual-luciferase reporter and
RNA immunoprecipitation assays. The protein
expression of ABCC1 was quantified by western blot
assay.
Results. Circ-CD44 was obviously upregulated in
OXA-resistant colorectal cancer tissues and cells. Lossof-function experiments revealed that inhibition of circCD44 suppressed proliferation, migration, and invasion
while it increased OXA sensitivity and apoptosis in
OXA-resistant colorectal cancer cells, which was
overturned by suppression of miR-330-5p; besides,
silencing of circ-CD44 also slowed the tumor growth in
vivo. Additionally, overexpression of miR-330-5p
inhibited chemotherapy resistance, proliferation,
migration, and invasion while it induced apoptosis by
targeting ABCC1.
Conclusion. Mechanistically, circ-CD44 functioned
as a miRNA sponge for miR-330-5p to upregulate the
expression of ABCC1 and regulate chemotherapy
resistance in CRC cells
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Citation
Histology and Histopathology Vol. 38, nĀŗ2 (2023)
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Este Ćtem estĆ” sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/