promotes migration, invasion and mediates osimertinib resistance in non-small cell lung cancer cell line.

BACKGROUND

It has been shown that circular RNAs (circRNAs) are involved in the pathogenesis of non-small cell lung cancer (NSCLC). However, the molecular mechanisms of circRNAs in tumor malignant progression and tyrosine kinase inhibitors (TKI) resistance remain undefined. Hereby, we explored the mechanisms by which promotes NSCLC progression and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) resistance.

METHODS

Transcriptome sequencing (RNA-seq) was carried out to obtain the we investigated. Quantitative reverse transcriptase-polymerase chain reaction was performed to detect the expression of . Cell counting kit-8 assay was performed to detect cell proliferation as well as flow cytometry to detect cell cycle and apoptosis. Transwell assay was performed to detect cell migration and invasion. tumourigenesis assays were performed to further validate the function of . The transcriptome was sequenced after RNA-pulldown and knockdown of cirRBM33 to identify the proteins bound by cirRBM33 and the downstream mechanisms involved in the regulation of cirRBM33.

RESULTS

The sequencing results revealed that cirRBM33 was highly expressed in the cell line of osimertinib resistant H1975. functional validation demonstrated that knockdown of inhibited H1975 proliferation, migration and invasion, changed cell cycle and promoted apoptosis. , knockdown of inhibited tumour growth. Mass spectrometry results and sequencing analysis of knockdown suggest that may mediate resistance to osimertinib in H1975-OR cells through regulate the DNMT1/interleukin-6 (IL-6) axis.

CONCLUSIONS

CircRBM33 is upregulated in NSCLC and that knockdown of inhibits the progression of NSCLC. may combine with DNMT1, and regulate the resistance of H1975 osimertinib-resistant cells to osimertinib that mediated by IL6. is a promising diagnostic and prognostic marker to provide effective treatment strategies for NSCLC patients.