SHARPIN overexpression promotes TAK1 expression and activates JNKs and NF-κB pathway in Mycosis Fungoides.

Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphomas (CTCL). Shank-associated RH domain-interacting protein participates in the initiation and development of multiple tumors. However, the clinical significance of in MF hasn't been investigated. The c-Jun N-terminal kinases (JNKs) pathway is a member of mitogen-activated protein kinases (MAPKs). Its dysregulation is observed in various tumors including CTCL, whereas the roles of JNKs pathway in MF remain largely unknown, the relationship between SHduanyu37IN and JNKs pathway remains elusive. Herein, we showed that upregulated expression of SHduanyu37IN was related to poor prognosis of MF patients. In vitro experiments found increased SHduanyu37IN expression and activation of JNKs pathway in MF cell line MyLa2059. SHduanyu37IN induced transforming growth factor β activated kinase-1 (TAK1) transcription, which is an upstream kinase of JNKs, NF-κB and p38 pathway, leading to activation of JNKs and NF-κB pathway. SHduanyu37IN also promoted p38 signalling independent of TAK1 expression, by which overexpression of SHduanyu37IN induced cell proliferation, inhibited apoptosis, enhanced migration and invasion of MyLa2059. Our work provided direct evidences for effects of SHduanyu37IN on JNKs and NF-κB pathway, and the contributing roles of JNKs, NF-κB and p38 pathway regulated by SHduanyu37IN in the development of MF.

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