乳腺癌中miR-221、miR-222表达水平对GATA3和FOXA1蛋白的影响及其作用机制

doi:10.3969/j.issn.1004-616x.2021.06.006

Abstract

Abstract: OBJECTIVE: To investigate effects and mechanisms of miR-221 and miR-222 levels on expression of GATA3 and FOXA1 in invasive ductal carcinoma of breast cancers. METHODS: Invasive ductal carcinoma of breast cancer and their adjacent tissue samples were collected from January 2020 to May 2021 in the Cancer Hospital of Shantou University. Expression levels of miR-221/222 were detected by Stem-loop real-time PCR and expression of GATA3 and FOXA1 were detected by immunohistochemistry in both tissues. Correlations between expression levels of miR-221/222,GATA3 and FOXA1,as well as the relation between their expression levels and clinicopathological characteristics were analyzed. Furthermore,expression levels of miR-221/222 were detected by qRT-PCR in five breast cancer cell lines and MCF-7 cells after transfection with miR-221/222 mimics. Meanwhile,protein expression of GATA3,FOXA1,ER-α and E-cadherin were analyzed by Western blot. The abilities cell scratch repair,and migration and invasion of the cells were detected by both wound healing and transwell assays. RESULTS: Among the 86 cases,expression levels of miR-221 and miR-222 in breast invasive ductal carcinoma were significantly higher than that in adjacent tissues (P=0.00). Expression levels of miR-221/222 were significantly higher in the negative expression group of GATA3,FOXA1,ER-α and PR compared with the positive expression group (P<0.01). miR-221/222 expression levels were significantly increased in breast cancer of positive expression of Her-2 and high expression of Ki-67 compared with the negative expression of Her-2 and low expression of Ki-67 (P<0.05). miR-221/222 expression levels were also significantly higher in triple negative breast cancer and Her-2 positive subtypes than that in Luminal A and Luminal B1 subtypes (P=0.00). No association was found between miR-221/222 expression levels with age,menopausal status,tumor size,histological grade,lymph node metastasis,and TNM stage. In all 5 breast cancer cell lines,expression of miR-221/222 was one of the lowest in MCF-7 cells. Compared with the control group,the expression of miR-221/222 was significantly increased after transfection with miR-221/222 mimics in MCF-7 cells (P<0.05),and endogenous GATA3 and FOXA1 protein expressions were inhibited in cells (P<0.01). Expression of ER-α and E-cadherin decreased significantly (P<0.01). The ability of scratch repair and migration and invasion were significantly enhanced (P<0.01). CONCLUSION: miR-221/222 might promote migration and invasion in breast cancers by down-regulating expressions of GATA3,FOXA1,and ER-α.

Key words: breast cancer, miR-221, miR-222, GATA3, FOXA1, stem-loop qPCR

CLC Number:

R737.9

FANG Yutong, ZHANG Qunchen, HONG Chaoqun, CHEN Chunfa, CHEN Jiongyu, ZHANG Rendong, WU Jundong. Mechanisms of miR-221 and miR-222 on expression of GATA3 and FOXA1 and their effects in breast cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 435-441,460.

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Mechanisms of miR-221 and miR-222 on expression of GATA3 and FOXA1 and their effects in breast cancer

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