Open Access

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

  • Authors:
    • Yao Yang
    • Yan‑Hua Liang
    • Yan Zheng
    • Ling‑Jie Tang
    • Si‑Tong Zhou
    • Jing‑Na Zhu
  • View Affiliations

  • Published online on: February 7, 2020     https://doi.org/10.3892/mmr.2020.10981
  • Pages: 1799-1808
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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April-2020
Volume 21 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yang Y, Liang YH, Zheng Y, Tang LJ, Zhou ST and Zhu JN: SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN. Mol Med Rep 21: 1799-1808, 2020.
APA
Yang, Y., Liang, Y., Zheng, Y., Tang, L., Zhou, S., & Zhu, J. (2020). SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN. Molecular Medicine Reports, 21, 1799-1808. https://doi.org/10.3892/mmr.2020.10981
MLA
Yang, Y., Liang, Y., Zheng, Y., Tang, L., Zhou, S., Zhu, J."SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN". Molecular Medicine Reports 21.4 (2020): 1799-1808.
Chicago
Yang, Y., Liang, Y., Zheng, Y., Tang, L., Zhou, S., Zhu, J."SHARPIN regulates cell proliferation of cutaneous basal cell carcinoma via inactivation of the transcriptional factors GLI2 and c‑JUN". Molecular Medicine Reports 21, no. 4 (2020): 1799-1808. https://doi.org/10.3892/mmr.2020.10981