A Study On Long Non-coding RAN BANCR Associated With EGFR-TKI Resistance In Non-small Cell Lung Cancer

Background:Currently,lung cancer is one of the most common malignancies worldwide.Globally,it is estimated that there were 2.094 million new cases of lung cancer,accounting for 11.6% of the total number of cancer cases and 1.761 million deaths and accounting for 18.4% of the total number of cancer deaths in 2018.It ranks first among all malignant tumors in terms of both morbidity and mortality.In recent years,the incidence and mortality of lung cancer in China have shown a significant increase.In China,it is estimated that there were 774,000 new cases of lung cancer,accounting for 18.1% of the total cases of cancer and 691,000 deaths and accounting for 24.1% of the total deaths from cancer in 2018.It ranks first among all malignant tumors in terms of both morbidity and mortality.Non-small cell lung cancer(NSCLC)is the main type of lung cancer,accounting for about 80% to 85% of the total number of lung cancers,and more than 65% of patients are in the advanced stage.Epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)is the first-line standard treatment for NSCLC patients with EGFR mutation,but most patients inevitably develop resistance after a period of treatment.How to overcome EGFR-TKI resistance is an urgent problem at present.In recent years,a large number of studies have pointed out that in a variety of tumor cells,long-chain non-coding RNA(lnc RNA)BANCR has the role of tumor suppressor genes.The lnc RNA BANCR regulates gene expression through multiple pathways and is closely related to tumor development,invasion and metastasis and prognosis.However,the correlation between long non-coding RNA BANCR and EGFR-TKI resistance in non-small cell lung cancer remains unclear.Objective:To investigate the association of long non-coding RNA BANCR with EGFR-TKI resistance in non-small cell lung cancer and the underlying potential mechanism of action.Methods:Cell line PC9 with EGFR 19 exon deletion mutation and EGFR-TKI gefitinib-induced resistant cell line PC9/GR were selected for the study.(1)The expression differences of BANCR in PC9 and PC9/GR cells were detected by real-time PCR(q RT-PCR).(2)After overexpression of BANCR in PC9/GR cells,CCK-8 assay was used to detect the sensitivity of cells to gefitinib,colony formation assay was used to detect cell proliferation capacity,and flow cytometry was used to detect apoptosis.(3)After overexpression of BANCR in PC9/GR cells,the expression of EMT-related proteins in PC9/GR cells was detected by Western blot.Results:(1)BANCR expression was significantly lower in PC9/GR cells(P < 0.05).(2)BANCR was overexpressed in PC9/GR cells.Compared with the control group,the half inhibition concentration(IC50)of gefitinib on PC9/GR/BANCR cells decreased(P<0.05);the proliferation capacity of PC9/GR/BANCR cells was weakened;the apoptosis of PC9/GR/BANCR cells increased after gefitinib treatment(P < 0.05).(3)Western blot results showed that the expression level of E-cadherin significantly increased and the expression level of N-cadherin significantly decreased in PC9/GR/BANCR cells compared with the blank control group(P <0.05).Conclusion:Long non-coding RNA BANCR can inhibit PC9/GR cell proliferation and induce apoptosis,overexpression of BANCR can increase the sensitivity of PC9/GR cells to gefitinib and reverse their drug resistance,and the mechanism may be achieved through the regulation of EMT process.The present study has shown that the long non-coding RNA BANCR may be a new target for NSCLC treatment.