Abstract
Objective This investigation aimed to figure out the relation between discs large homolog 3 (DLG3) expression and the progression and prognosis of breast cancer (BC). Methods qRT-PCR was utilized for confirming DLG3 expression and RAC1 mRNA expression in BC tissues and cells. Subsequently, after overexpression or interference of DLG3, the changes of the biological activities of BC cells, including cell proliferation, migration, invasion, and apoptosis, were detected through CCK-8, colony formation assay, wound healing assay, transwell assay, and flow cytometry, respectively. Furthermore, western blotting was utilized to measure the protein expression of DLG3 and RAC1, as well as related proteins of epithelial-mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. Results At both cellular and tissue level in BC, DLG3 was downregulated and methylation level was upregulated; RAC1 showed an opposite change and was of a negative correlation with DLG3. In MCF-7 and HCC1937, we found that the upregulation of DLG3 could inhibit RAC1 expression as well as cell proliferation, invasion, migration, and EMT, while promoting apoptosis. Also, DLG3 inhibited the activation of the P13K/AKT pathway. Conclusion Hypermethylation of DLG3 promoter upregulates RAC1 and activates the PI3K/AKT pathway, thus promoting BC progression. This conclusion provides ideas and experimental basis for improving and treating BC patients.
Highlights
Among all malignant tumors in females, breast cancer (BC) is described as the most common one [1], and it is the second most fatal cancer accounting for 14% of all cancer-related deaths [2]. e incidence of BC, as in most other countries, is high in the Chinese female population, with new cases accounting for 12.2% of global new cases; Chinese BC patients account for 9.6% of all BC-caused deaths in the world [3]
Downregulation of discs large homolog 3 (DLG3) and Hypermethylation of Its Promoter Region in BC. e results of qRT-PCR and western blot confirmed that DLG3 mRNA and protein had lower expression in BC tissues (Figure 1(a) and 1(b)); at the cellular level, qRT-PCR revealed the downregulation of DLG3 in BC cells in comparison with MCF10A (Figure 1(c))
Bisulfite sequencing PCR indicated that by comparison with the normal group, the DNA methylation level of DLG3 in the BC tissue group showed a marked upregulation (Figure 1(d)); a similar increase was found in BC cells (Figure 1(e)). e lowest DLG3 expression was found in MCF-7 and the highest in HCC1937. erefore, these two kinds of BC cells were selected for the following experiments
Summary
Among all malignant tumors in females, breast cancer (BC) is described as the most common one [1], and it is the second most fatal cancer accounting for 14% of all cancer-related deaths [2]. e incidence of BC, as in most other countries, is high in the Chinese female population, with new cases accounting for 12.2% of global new cases; Chinese BC patients account for 9.6% of all BC-caused deaths in the world [3]. E incidence of BC, as in most other countries, is high in the Chinese female population, with new cases accounting for 12.2% of global new cases; Chinese BC patients account for 9.6% of all BC-caused deaths in the world [3]. Biological factors refer to heredity, infection, or gene mutation, which probably lead to the transformation of a normal breast cell into a cancer cell [4]. Treatment options for BC depend on the specific molecular subtype. While surgical techniques and treatment regimens have made advancement, BC patients are still prone to recurrence and metastasis, which are the main cause of their death [2, 6]. Erefore, it is vital to deeply understand the molecular mechanism of BC progression, so as to realize the prevention, diagnosis, and treatment of this disease While surgical techniques and treatment regimens have made advancement, BC patients are still prone to recurrence and metastasis, which are the main cause of their death [2, 6]. erefore, it is vital to deeply understand the molecular mechanism of BC progression, so as to realize the prevention, diagnosis, and treatment of this disease
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