Histol Histopathol, Vol 38, Zhao et al.

Circular RNA circ-CD44 regulates chemotherapy resistance by targeting the miR-330-5p/ABCC1 axis in colorectal cancer cells

Shuai Zhao*, Fei Xu*, Yiding Ji, Yuanyuan Wang, Ming Wei and Like Zhang

Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China
*These authors contributed equally to this paper

Corresponding Author: Ming Wei, Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, No.89 Donggang Road, Shijiazhuang 050031, Hebei Province, China. e-mail: pngdwq@163.com or Like Zhang, Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, No.89 Donggang Road, Shijiazhuang 050031, Hebei Province, China. e-mail: sn7eny@126.com

Summary. 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 circ-CD44 is investigated in CRC.
Methods. The expression levels of circ-CD44, miR-330-5p, 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-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. Colony-forming 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. Loss-of-function experiments revealed that inhibition of circ-CD44 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. Histol Histopathol 38, 209-221 (2023)

Key words: circ-CD44, miR-330-5p, ABCC1, CRC, OXA

DOI: 10.14670/HH-18-516