Abstract
Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF‐7 cells and increase the proportion of MCF‐7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA‐MB‐231 cells and increased the proportion of MDA‐MB‐231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG‐132 showed that IQUB activated Akt to promote GSK3β phosphorylation, which in turn activated Wnt/β‐catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.
Highlights
According to the Tumor Epidemiology Survey in 2017, breast cancer has become the highest incidence of women’s cancer in American, which seriously affects the health of women.[1]
We noticed that the expression of IQUB in breast cancer tissues was significantly increased, and positively correlated with the pathological differentiation of breast cancer, suggesting that IQUB may have a bearing on the malignant progression and prognosis of breast cancer
Overexpression of IQUB could significantly enhance the proliferation and migration ability of breast cancer cells, whereas knockdown of IQUB showed the opposite effect. These results suggested that IQUB acted as oncogene in the development of breast cancer
Summary
According to the Tumor Epidemiology Survey in 2017, breast cancer has become the highest incidence of women’s cancer in American, which seriously affects the health of women.[1] In China, there was an estimated 0.27 million breast cancer cases which leaded to 0.07 million deaths in 2015.2 Breast cancer patients mainly died of cancer metastasis; Kai Li, Yan-bin Ma and Zun Zhang contributed to this study We further explored the mechanism of IQUB in promoting breast cancer by activating the Akt/GSK3β/β-catenin signaling pathway, which would provide a new idea for better comprehension of breast cancer pathogenesis and breast cancer targeted therapy
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