Study on the mechanism of miR-96-5p targeting HOXA9 to promote the proliferation and invasion of breast cancer cells
Objective To explore the mechanism of miR-96-5p targeted homeobox A9(HOXA9)promoting the pro-liferation and invasion of breast cancer cells.Methods Samples and complete clinical data of 60 cases of breast cancer and paracancerous tissues were resected from September 2022 to December 2022 were collected.Two pairs of differentially ex-pressed miRNA in breast cancer and paracancerous tissues were analyzed by miRNA microarray.The expression of miR-96-5p in breast cancer,paracancerous tissues and breast cancer cell lines was detected by qRT-PCR,and the relationship between miR-96-5p expression and clinicopathological features was analyzed.The effects of miR-96-5p on breast cancer cells MDA-MB-231 and MCF-7 were detected by MTT,clone formation,EdU method,scratch,Transwell test and xenotransplanta-tion in vivo.Analysis and prediction of the targeting relationship between miR-96-5p and HOXA9.Detection of HOXA9 and Wnt/β-catenin signal pathway protein expression in tumor,paracancerous tissues and breast cancer cells by WB.Statistics of tumor volume,mass and number of liver metastases in nude mice.The expression of HOXA9 and β-catenin were detected by immunohistochemistry.Results The results of qRT-PCR detection showed that the level of miR-96-5p in breast cancer tissue increased and the level of HOXA9 decreased(P<0.05).The patients with high expression of miR-96-5p was associated with tumor size ≥ 3 cm,positive lymph node metastasis and TNM stage Ⅲ-Ⅳ(P<0.05).Inhibition of miR-96-5p expression de-creased the proliferation,clone formation,migration,invasion,Wnt-1,β-catenin,Cyclin D1 expression level,tumor volume,mass and number of liver metastases in nude mice(P<0.05),and increased HOXA9 expression level(P<0.05).miR-96-5p targeted regulated HOXA9 expression.Overexpression of HOXA9 can reverse the promoting effect of miR-96-5p on malignant biological behavior of breast cancer cells.Conclusion miR-96-5p activates the Wnt/β-catenin signaling pathway by inhibiting HOXA9 expression and promotes the development of breast cancer.