Mechanism Research Of LGALS3BP In Regulating Sensitive To Adriamycin Therapy Of HR+/HER2-breast Cancer

OBJECTIVE:Explore the role and mechanism of LGALS3 BP in regulating sensitive to adriamycin therapy of HR+/HER2-breast cancer.Methods:1.Firstly,bioinformatics analysis was used to explore the expression of LGALS3 BP in HR+/HER2-breast cancer adriamycin-resistant cells and breast cancer tissues,then the relationship between the expression of LGALS3 BP and the prognosis of HR+/HER2-breast cancer was explored.2.Si RNAs were used to knock down LGALS3 BP in MCF-7 and T47 D breast cancer cell lines.The changes of cell proliferation ability and sensitivity of DOX were demonstrated by colony formation,Ed U and CCK8 assay.Western blot was used to analyze the changes of apoptosis-related biomarkers.3.Transcriptome sequencing of LGALS3 BP knockdown cells and parental cells was performed to screen the possible downstream pathways and candidates.6.STAT1 was selected as the possible downstream of LGALS3 BP,and the verification of its regulatory relationship with LGALS3 BP were q PCR and western blot.RESULT:1.LGALS3 BP is highly expressed in HR+/HER2-breast cancer DOX-resistant cells and breast cancer tissues.High expression of LGALS3 BP was associated with shorter RFS,OS,and DMFS.2.LGALS3 BP promotes breast cancer cell proliferation,and knockdown of LGALS3 BP increases sensitivity of DOX.3.After transcriptome sequencing,functional enrichment analysis showed that LGALS3 BP was related to virus defense response,regulation of cell response to interferon,JAK-STAT signaling pathway and cytokine-cytokine receptor interaction pathway.Apoptosis pathway and necrotic apoptosis pathway were activated after knocking down LGALS3 BP.4.The expression of STAT1 is negatively regulated by LGALS3 BP,and knockdown of LGALS3 BP activates the expression of p-STAT1(Tyr701).CONCLUSION:LGALS3BP promotes breast cancer cells proliferation,and inhibiting the expression of LGALS3 BP can increase the sensitivity of breast cancer cells to DOX.The possible mechanism is LGALS3 BP negatively regulates the expression of STAT1 and its phosphorylation activation at Tyr701.