Study on the relationship between miR-22-3p,ERBB3 expression,epithelial-Mesenchymal transition,and prognosis in cervical cancer tissues
Sun Guifeng
Yang Zhihui
Yin Xiaoying
Pan Shumei
Yin Zhengjin
Cao Xiaohui
Zhang Ying
Abstract：Objective To investigate the relationship between the expression of microRNA-22-3p(miR-22-3p),Erb-B2 receptor tyrosine kinase 3(ERBB3),epithelial-mesenchymal transition(EMT),and prognosis in cervical cancer(CC)tis-sues.Methods A total of 154 CC patients who underwent total or radical hysterectomy at the Department of Obstetrics and Gynecology,Eastern Theater General Hospital,from January 2018 to June 2021 were selected.The expression levels of miR-22-3p,ERBB3,and EMT markers(N-cadherin,E-cadherin,SNAI1,Vimentin)in CC tissues and matched adjacent normal tissues were detected using real-time quantitative PCR.The binding site of miR-22-3p and ERBB3 was predicted through an online database.Pearson correlation analysis was used to assess the correlation between the expression of miR-22-3p,ERBB3,and EMT markers in CC tissues.Based on the mean expression levels of miR-22-3p and ERBB3 in CC tissues,patients were divided into high-expression and low-expression groups.Kaplan-Meier survival curves were plotted for progres-sion-free survival based on different miR-22-3p and ERBB3 mRNA expressions.Multivariate Cox regression analysis was per-formed to evaluate the relationship between miR-22-3p and ERBB3 mRNA expression and prognosis in CC patients.Results Compared with adjacent normal tissues,CC tissues showed lower expression of miR-22-3p and E-cad mRNA,but higher ex-pression of ERBB3 mRNA,N-cad mRNA,SNAI1 mRNA,and VIM mRNA(t/P=-29.759/＜0.001,-30.944/＜0.001,36.216/＜0.001,35.503/＜0.001,22.026/＜0.001,36.849/＜0.001).A binding site between miR-22-3p and ERBB3 was found at the 3' un-translated region(positions 36-43).In CC tissues,miR-22-3p was negatively correlated with ERBB3 mRNA,N-cad mRNA,SNAI1 mRNA,and VIM mRNA,but positively correlated with E-cad mRNA(r/P=-0.795/＜0.001,-0.744/＜0.001,-0.681/＜0.001,-0.761/＜0.001,0.756/＜0.001);ERBB3 mRNA was positively correlated with N-cad mRNA,SNAI1 mRNA,and VIM mRNA,and negatively correlated with E-cad mRNA(r/P=0.741/＜0.001,0.680/＜0.001,0.730/＜0.001,-0.768/＜0.001).Lower expression of miR-22-3p and higher expression of ERBB3 mRNA were observed in poorly differentiated tumors,FIGO stageⅢ,and cases with lymph node metastasis compared to moderately/highly differentiated tumors,FIGO stage Ⅰ-Ⅱ,and those without lymph node metastasis(t/P=2.907/0.004,3.092/0.002,3.485/0.001,2.891/0.004,3.113/0.002,3.505/0.001).The 3-year progression-free survival rate for the 154 CC patients was 65.58％(101/154).Patients with high miR-22-3p expression had a higher 3-year progression-free survival rate compared to those with low expression,while patients with high ERBB3 mRNA expression had a lower 3-year progression-free survival rate compared to those with low expression(x2/P=17.390/＜0.001,16.122/＜0.001).Poor differentiation,FIGO stage Ⅲ,lymph node metastasis,and ERBB3 mRNA ≥2.39 were independent risk factors for tumor progression in CC patients,while miR-22-3p ≥ 1.32 was an independent protective factor[OR(95％CI)=3.500(1.820-6.731),2.309(1.111-4.798),4.403(2.224-8.716),4.237(1.987-9.037),0.318(0.157-0.644)].Conclusion Low expression of miR-22-3p and high expression of ERBB3 mRNA in CC tissues are associated with poor pathological fea-tures,EMT,and prognosis,and they may serve as novel biomarkers for assessing EMT and prognosis in CC patients.
Keywords：Cervical cancerMicroRNA-22-3pErb-B2 receptor tyrosine kinase 3Epithelial-mesenchymal transitionPrognosis
Publication Date：2025-07-18
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 848-854 )