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'-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.