SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN.

SHANK‑associated RH domain‑interacting protein is a component of the linear ubiquitin chain assembly complex that can enhance the NF‑κB and JNK signaling pathways, acting as a tumor‑associated protein in a variety of cancer types. The present study investigated the role of in cutaneous basal cell carcinoma (BCC). Human BCC (n=26) and normal skin (n=5) tissues, and BCC (TE354.T) and normal skin (HaCaT) cell lines were used to evaluate SHduanyu37IN expression level using immunohistochemistry and western blotting, respectively. A lentivirus carrying or negative control short hairpin RNA was infected into TE354.T cells, and the infected stable cells were assayed to analyze tumor cell proliferation, cell cycle, apoptosis, migration and invasion by Cell Counting Kit‑8 and 5‑ethynyl‑2'‑deoxyuridine incorporation assays, flow cytometry and Transwell assays. Western blotting was performed to assess the protein expression levels of gene signaling in BCC cells. SHduanyu37IN protein expression levels were downregulated or absent in BCC cancer nests and precancerous lesions compared with normal skin samples. In addition, SHduanyu37IN expression levels were lower in TE354.T cells compared with HaCaT cells. SHduanyu37IN shRNA enhanced tumor cell proliferation and the S phase of the cell cycle, whereas BCC cell apoptotic rates, and migratory and invasive abilities were not significantly altered. The expression levels of cyclin D1, cyclin‑dependent kinase 4, phosphorylated‑c‑JUN and GLI family zinc finger 2 proteins were increased, whereas Patched 1 (PTCH1) and PTCH2 were decreased in the BCC cells. Therefore, the present results suggested that SHduanyu37IN may act as a tumor suppressor during BCC development.

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