1. SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c-JUN
- Author
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Yao Yang, Si‑Tong Zhou, Ling‑Jie Tang, Jing‑Na Zhu, Yan Zheng, and Yan‑Hua Liang
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Skin Neoplasms ,SHANK-associated RH domain-interacting protein ,Proto-Oncogene Proteins c-jun ,Cell ,Nerve Tissue Proteins ,Zinc Finger Protein Gli2 ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Cell Line, Tumor ,GLI family zinc finger 2 ,Genetics ,medicine ,Humans ,Molecular Biology ,integumentary system ,Cell growth ,Chemistry ,cutaneous basal cell carcinoma ,c-jun ,c-JUN ,Articles ,Cell cycle ,Middle Aged ,Molecular biology ,PTCH2 ,Gene Expression Regulation, Neoplastic ,HaCaT ,030104 developmental biology ,medicine.anatomical_structure ,cell proliferation ,Oncology ,Cell culture ,Carcinoma, Basal Cell ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,Signal Transduction - Abstract
SHANK‑associated RH domain‑interacting protein (SHARPIN) 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 SHARPIN 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 SHARPIN expression level using immunohistochemistry and western blotting, respectively. A lentivirus carrying SHARPIN‑targeting 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 SHARPIN‑silenced BCC cells. SHARPIN protein expression levels were downregulated or absent in BCC cancer nests and precancerous lesions compared with normal skin samples. In addition, SHARPIN expression levels were lower in TE354.T cells compared with HaCaT cells. SHARPIN 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 SHARPIN‑shRNA‑infected BCC cells. Therefore, the present results suggested that SHARPIN may act as a tumor suppressor during BCC development.
- Published
- 2020