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Archive > Volume 30 Issue 7 > 2023,30(7):594-602. DOI:10.3872/j.issn.1007-385X.2023.07.007 Prev Next
Basic Research
Transcription factor BATF3 promotes malignant biological behavior of clear cell renal cell carcinoma cells by regulating vimentin
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Abstract:
Objective: To investigate the expression of basic leucine zipper ATF-like transcription factor 3 (BATF3) in clear cell renal cell carcinoma (ccRCC) and the molecular mechanism of its regulation of malignant biological behavior of ccRCC cells. Methods: ccRCC tissues and para-cancerous tissues were collected from 64 ccRCC patients who underwent surgical treatment at the 980th Hospital of the Joint Logistics Support Force of PLA from March 2019 to January 2022. The expression of BATF3 mRNA in ccRCC tissues, para-cancerous tissues, renal carcinoma ACHN and 786-O cells was determined by qPCR. The expressions of BATF3 protein in ccRCC tissues and para-cancerous tissues were determined by immunohistochemistry and the relationship between the expressions and the clinicopathologic characteristics was analyzed. BATF3 knockdown and over-expression plasmids were constructed and transfected into 786-O and ACHN cells, and the effects of BATF3 on the proliferation, migration and invasion of 786-O cells or ACHN cells were determined by MTS and Transwell assays. The effects of BATF3 on the expressions of related epithelial-mesenchymal transition (EMT) genes of 786-O and ACHN cells were detected by qPCR. CHIP and dual luciferase reporter assay were performed to detect the binding of BATF3 as a transcription factor to vimentin (VIM) and regulate its transcription. The effects of simultaneous over-expression of BATF3 and knockdown of VIM on the proliferation, migration and invasion ability of 786-O cells were determined by MTS and Transwell assays. Results: Compared with para-cancerous tissues, BATF3 mRNA and protein expressions were markedly higher in ccRCC tissues (all P<0.01) and the expression level of BATF3 mRNA was closely correlated with the degree of differentiation of ccRCC and its TNM stage (all P<0.01). Compared with normal renal epithelial cells 293T, the expression of BATF3 was significantly higher in ccRCC cells ACHN and 786-O (all P<0.01). Knockdown of BATF3 expression significantly inhibited the proliferation,migration and invasion ability of 786-O cells (all P<0.01). Over-expression of BATF3 significantly promoted the proliferation,migration and invasion ability of ACHN cells (all P<0.01). Knockdown or overexpression of BATF3 inhibited the expression of EMT-related genes in 786-O cells or promoted the expression of EMT-related genes in ACHN cells (all P<0.01). BATF3 could bind to sites in the upstream promoter region of VIM and directly regulate the transcription expression of VIM. Simultaneous overexpression of BATF3 and knockdown of VIM reversed the effects of over-expression of BATF3 on the proliferation, migration and invasion ability of 786-O cells. Conclusion: BATF3 was highly expressed in ccRCC tissues and was closely related to its differentiation degree and TNM stage. BATF3 directly regulated the expression of VIM, which in turn regulated the malignant biological behavior of ACHN and 786-O cells. Therefore, it could be used as a potential target for clinical treatment of ccRCC.
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