Abstract
Metastasis is the leading cause of lung cancer-associated death. Downregulated expression of E-cadherin followed by epithelial-mesenchymal transition (EMT) is critical for metastasis initiation in lung cancer. BTBD7 plays essential roles in lung cancer metastasis, but the mechanisms remain unknown. This study aimed to investigate the relationship between BTBD7 and E-cadherin in lung cancer and explore the role of BTBD7 in EMT. Fresh lung cancer and paracancer tissue specimens were collected from 30 patients, and the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin was analyzed by qRT-PCR, western blotting, and immunohistochemistry. A549 and HBE cells were cultured and treated with TGF-β1 for 72 h to induce EMT. Western blotting and qRT-PCR were performed to evaluate the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin. Then, A549 cells were treated separately with the BTBD7-ENTER plasmid, BTBD7-siRNA, and paclitaxel. After TGF-β1-induced EMT, the abovementioned markers were analyzed by western blotting and qRT-PCR. Wound healing assays were applied to assess the migration ability of cells in different groups. For animal experiments, A549 cells transfected with the BTBD7-ENTER plasmid were transplanted into BALB/c nude mice. After 4 weeks, all nude mice were sacrificed, and tumor tissues were harvested for qRT-PCR, western blot, and immunohistochemical analyses of the abovementioned markers. All experimental results showed that the levels of BTBD7, N-cadherin, fibronectin, and vimentin were increased in lung cancer tissues and cells, while the E-cadherin level was decreased. Transfection experiments showed that BTBD7 inhibited E-cadherin expression and enhanced EMT. Moreover, the migration capacity of lung cancer cells was increased by the high level of BTBD7. We concluded that BTBD7 is highly expressed during lung cancer development and metastasis and can inhibit the expression of E-cadherin and promote EMT in lung cancer. BTBD7 may thus be a therapeutic target for lung cancer.
Highlights
Lung cancer is a leading cause of cancer-related death worldwide, accounting for approximately 28% of cancerrelated deaths [1–3]
Epithelial-mesenchymal transition (EMT) has a common cytological mechanism: proteins associated with epithelial properties, such as E-cadherin and β-catenin, are downregulated, and proteins associated with mesenchymal properties, such as vimentin, fibronectin (FN), and N-cadherin, are upregulated; β-catenin enters the nucleus; and cells undergo cytoskeletal changes, gaining a strong capacity for migration [5–7]
Expression of BTBD7 and EMT Markers Is Increased in Cancer Tissues, while E-Cadherin Expression Is Decreased
Summary
Lung cancer is a leading cause of cancer-related death worldwide, accounting for approximately 28% of cancerrelated deaths [1–3]. Great progress has been made in the prevention and treatment of cancer, the mechanism underlying cancer is still unclear, the rate of cancer mortality remains high, and the 5-year survival rate is quite low—only 17% [3]. Recurrence, metastasis, and drug resistance are common causes of lung cancer treatment failure. Erefore, studying the mechanism of lung cancer development and developing new targeted drugs to block the development of lung cancer are of great importance in improving the cure rate and survival rate of lung cancer patients. EMT has a common cytological mechanism: proteins associated with epithelial properties, such as E-cadherin and β-catenin, are downregulated, and proteins associated with mesenchymal properties, such as vimentin, fibronectin (FN), and N-cadherin, are upregulated; β-catenin enters the nucleus; and cells undergo cytoskeletal changes, gaining a strong capacity for migration [5–7]. Epithelial-derived malignant cells lose their tight junction
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