VAV1 regulates cell growth in cutaneous T-cell lymphoma via the BAMBI/BMF signalling pathway.

Abstract

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of tumours originating from the cutaneous infiltration of clonal malignant T cells. VAV1 is a hematopoietic signal transducer and an oncogene in various cancers, however, the relevance of aberrant VAV1 expression in CTCL pathogenesis remains unclear. This study aimed to evaluate the expression pattern and underlying pathogenic mechanisms of VAV1 in CTCLs. The expression of VAV1 in CTCL tumour tissues and benign inflammatory dermatoses skin samples were examined by immunohistochemistry. CTCL cells were also transfected with lentiviral-based VAV1 gene knockdown vectors, and the effects of VAV1 knockdown on cell proliferation and apoptosis in CTCL cells was determined by MTS assay and flow cytometry. Transcriptomic sequencing was performed to detect the direct downstream targets of VAV1 silencing. RT-qPCR and western blot analysis were used to verify the transcriptomic analysis results. High expression of VAV1 was observed in CTCL tissues (n = 25) compared with benign inflammatory dermatoses (n = 23) using immunohistochemistry. VAV1 knockdown in two CTCL cell lines decreased cell proliferation and increased the percentage of apoptotic cells. Moreover, messenger RNA and protein expression of Bcl-2-modifying factor was increased, whereas that of bone morphogenetic proteins and activin membrane-bound inhibitor was downregulated in VAV1-silenced CTCL cells. VAV1 silencing induces apoptosis and inhibits cell growth, which is associated with upregulation of Bcl-2 modifying factor and downregulation of bone morphogenetic proteins and activin membrane-bound inhibitor. Therefore, VAV1 may be a potential tumour marker and therapeutic target for CTCLs.