LINC00641调节miR-1306-5p/FGFR3轴对非小细胞肺癌H1299细胞恶性进展和化疗耐药性的影响OA

Background and objective Non-small cell lung cancer(NSCLC)is one of the causes of cancer-related deaths worldwide.Although platinum-based chemotherapy is the main treatment method for advanced patients,acquired resistance often leads to treatment failure.Long non-coding RNAs(lncRNAs)play an important role in tumor occurrence and development,but the specific mechanism of their involvement in chemotherapy resistance in NSCLC is not yet fully un-derstood.This study aims to explore the effect of LINC00641 on the microRNA-1306-5p(miR-1306-5p)/fibroblast growth factor receptor 3(FGFR3)axis on the malignant progression and chemotherapy resistance of NSCLC cell line H1299.Meth-ods The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR);and the interaction was verified by the dual-luciferase reporter gene assay.H1299 cells were randomly divided into the following groups:CG group(normal culture),sh-NC group(transfected with sh-NC),sh-LINC00641 group(transfected with sh-LINC00641),sh-LINC00641+anti-NC group(transfected with sh-LINC00641 and anti-NC),sh-LINC00641+anti-miR-1306-5p group(transfected with sh-LINC00641 and anti-miR-1306-5p),mimic-NC group(transfected with mimic-NC),miR-1306-5p-mimics group(transfected with miR-1306-5p-mimics),miR-1306-5p-mimics+OE-NC group(transfected with miR-1306-5p-mimics and OE-NC),and miR-1306-5p-mimics+OE-FGFR3 group(transfected with miR-1306-5p-mimics and OE-FGFR3).Then cell proliferation,migration,and invasion were measured by plate colony formation assay,scratch assay,and Transwell assay,respectively.In addition,H1299/DDP cells were grouped as mentioned above.After that,the chemotherapy resistance of H1299/DDP cells was detected by the MTTmethod.And Western blot was implemented to detect the protein expressions of FGFR3,proliferating cell nuclear antigen(PCNA),matrix metalloproteinase 13(MMP-13),integrin β1 in H1299 cells,and the P-glycoprotein(P-gp),multidrug resistance-associated protein 1(MRP1)in H1299/DDP cells.Results In NSCLC tis-sues or cells(H1299,H1299/DDP),LINC00641 and FGFR3 were highly expressed,while miR-1306-5p was lowly expressed,and the expression trends of these three factors changed more significantly in the drug-resistant cell line H1299/DDP(P<0.05).LINC00641 could negatively regulate miR-1306-5p in a targeted manner;and miR-1306-5p could negatively regulate FGFR3 in a targeted manner.Knockdown of LINC00641(sh-LINC00641)or overexpression of miR-1306-5p reduced the clone number,scratch healing rate,migration number,invasion number,and the expression of PCNA,MMP-13,and integrin β1 proteins in H1299 cells(P<0.05),and also suppressed the optical density(OD)540 value and the expression of P-gp and MRP1 proteins in H1299/DDP cells(P<0.05).In addition,inhibition of miR-1306-5p or overexpression of FGFR3 could reverse the inhibitory effects of LINC00641 knockdown or miR-1306-5p overexpression on the proliferation,migration,invasion,and chemoresistance of H1299 cells(P<0.05).Conclusion Knockdown of LINC00641 can regulate the miR-1306-5p/FGFR3 axis,inhibit the malignant progression and chemotherapy resistance of NSCLC cells,and provide a new candidate target for molecular intervention of chemotherapy resistance in NSCLC.