| Background and objective In recent years,the global incidence and mortality of breast cancer are increasing,which is a serious threat to women's health.Cell invasion and migration are the key factors that lead to tumor recurrence and affect prognosis.Breast cancer presents different phenotypes as a highly heterogeneous disease.Accurate treatment for different types has always been the direction of clinical efforts.Therefore,it is important to identify the key regulatory genes in the development of breast cancer and reliable and specific biomarkers for diagnosis and prognosis.PNO1 is a highly conserved ribosomal regulatory factor,which participates in ribosomal biogenesis and is related to human diseases and tumorigenesis.It has been demonstrated that the high expression of PNO1 is associated with poor prognosis of cancer.As a potential oncogene,it is involved in tumor growth and progression.However,there are relatively few studies on breast cancer.Therefore,we explore the role of PNO1 and its biological function in breast cancer to help finding new molecular therapeutic targets and therapeutic drugs for breast cancer.Methods(1)Bioinformatics was used to analyze the PNO1 expression level of different types of breast cancer.Kaplan-Meier survival analysis identifies the relationship between PNO1 expression and the overall survival rate(OS)and disease-free survival rate(DFS)with different pathological and immunohistochemical types.(2)Immunohistochemical method was used to verify the expression level of PNO1 in 195 clinical samples.Kaplan-Meier survival analysis to analyze the PNO1 expression and poor prognosis.Univariate and multivariate Cox regression were used to analyze the related risk factors and independent factors of breast cancer patients.(3)To construct MDA-MB-231 and MCF-7 breast cancer cell lines infected by lentivirus with overexpression and interference of PNO1.CCK8 and plate cloning tests were used to evaluate the effect of PNO1 on the proliferation of breast cancer cell lines.Scratch test and Transwell migration and invasion test were used to evaluate the effect of PNO1 on the migration and invasion of the two cell lines.Results(1)The expression of PNO1 m RNA in breast cancer tissues was significantly higher than that in para-cancerous tissues in TCGA database.Kaplan-Meier survival analysis revealed that PNO1 was correlated with the overall survival rate and disease-free survival rate.Meanwhile,the high expression of PNO1 was significantly correlated with OS and DFS in invasive ductal carcinoma,but not with invasive lobular carcinoma,and the high expression of PNO1 was correlated with OS and DFS in Hormone receptor(HR)positive type and HER negative patients(p< 0.05),but not with other types.(2)195 clinical breast cancer samples showed that the expression of PNO1 in breast cancer was significantly higher than that in adjacent tissues,and the high expression of PNO1 was significantly correlated with the poor prognosis of OS and DFS in breast cancer patients(p< 0.05),which was consistent with the results of TCGA data analysis.Univariate and multivariate analysis showed that the status of ER,PR and Ki67 could be used as independent factors affecting the survival of breast cancer patients,and the high expression of PNO1 was significantly correlated with the poor prognosis of OS and DFS in ER negative group.(3)The overexpression of PNO1 significantly promoted the proliferation and invasion ability of MDA-MB-231 breast cancer,while the deletion of PNO1 significantly weakened the proliferation and migration ability of MCF-7 cells by inhibiting cell proliferation and inducing apoptosis.Conclusion:(1)PNO1 can be used as a biomarker of breast cancer with different pathological types and different molecular types.(2)PNO1 can effectively supplement the existing pathological and immunohistochemical classification.(3)PNO1 plays an important role in the proliferation and invasion of breast cancer and can be an effective target for anti-metastasis therapy of breast cancer. |
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