CircMYBL2 regulates the resistance of cervical cancer cells to paclitaxel via miR‐665‐dependent regulation of EGFR

Abstract

Circular RNAs are considered to be associated with cancer resistance. This study aims to investigate the function and mechanism of circMYBL2 in paclitaxel (PTX) resistance of cervical cancer (CC). The expression of circMYBL2, miR-665 and epidermal growth factor receptor (EGFR) was investigated using quantitative real-time polymerase chain reaction assay. Cell viability, cell colony number, cell proliferation, apoptosis and lactate dehydrogenase (LDH) were detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, colony formation, 5-ethynyl-2 0 -deoxyuridine incorporation, flow cytometry and LDH release assays, respectively. The interaction between miR-665 and circMYBL2 or EGFR was confirmed by dual-luciferase reporter assay. The protein expression levels were quantified by western blot or immunohistochemistry assay. Mice xenograft models were constructed to investigate the effect of circMYBL2 on CC tumor growth. CircMYBL2 was upregulated in CC tissues and cells, especially in PTX-resistant CC tissues and cells, and it was a stable circRNA mainly distributed in the cytoplasm. CircMYBL2 could enhance the PTX resistance of CC cells in vitro and promote CC tumor growth in vivo. Mechanistically, circMYBL2 could inhibit the PTX sensitivity and promote cell malignant behaviors in PTX-sensitive and PTX-resistant CC cells via upregulating EGFR mediated by miR-665. CircMYBL2 played a positive role in the PTX resistance and malignant activities of PTX-sensitive and PTX-resistant CC cells by regulating the miR-665/EGFR network, providing a novel therapeutic strategy for the treatment of CC patients resistant to PTX.

Comparison of the clinical efficacy of paclitaxel + carboplatin and paclitaxel + cisplatin on tumor markers and WHOQOL-BREF score on cervical cancer patients

“…Consequently, this impedes mitosis and fosters the demise of tumor cells, yielding potent antitumor effects [16][17][18]. Relevant clinical studies have corroborated these findings, indicating that the preoperative utilization of paclitaxel in the treatment of cervical cancer patients can substantially reduce tumor size, facilitating the complete removal of tumor lesions during subsequent surgical procedures, subsequently diminishing the risk of recurrence and metastasis post-surgery [19,20]. Paclitaxel, cisplatin and carboplatin have all demonstrated individual effectiveness in the treatment of cervical cancer.…”

CircRNA_0044556 regulates paclitaxel resistance in triple-negative breast cancer by targeting miR-665

“…Importantly, recent studies have found that miR-665 is signi cantly downregulated in TNBC, and the upregulation of miR-665 is positively correlated with the survival time of patients with TNBC [16]. In addition, miR-665 is inextricably associated with paclitaxel resistance in cervical cancer cells [31]. However, the mechanism of miR-665 resistance to paclitaxel in TNBC remains unknown.…”

The role of long noncoding RNAs in therapeutic resistance in cervical cancer

“…Moreover, circMTO1 enhanced chemoresistance via sponging miR-6893 in cervical cancer ( Chen et al, 2019 ). CircMYBL2 governed paclitaxel resistance via targeting miR-665/EGFR axis in cervical cancer ( Dong et al, 2021 ). Hsa_circ_0074269 increased cisplatin resistance via mediating miR-485-5p and TUFT1 in cervical cancer ( Chen et al, 2022b ).…”