Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer
Authors Li P, Huang Z, Wang J, Chen W, Huang J
Received 16 November 2018
Accepted for publication 23 January 2019
Published 26 February 2019 Volume 2019:12 Pages 1603—1611
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 4
Editor who approved publication: Dr Takuya Aoki
Pengling Li,1,2 Ziming Huang,3 Jipeng Wang,2 Wei Chen,2 Jianan Huang1
1Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; 2Department of Respiratory Medicine, The Affiliated Huai’an No 1. People’s Hospital, Nanjing Medical University, Huai’an 223300, Jiangsu, China; 3Department of Emergency Surgery, The Affiliated Huai’an No 1. People’s Hospital, Nanjing Medical University, Huai’an 223300, Jiangsu, China
Background and objectives: Ubiquitin-specific peptidase 28 (USP28) has been reported to play significant roles in several tumors, but its roles in non-small-cell lung cancer (NSCLC) is still unknown. In this study, we aimed to investigate the biological function and molecular mechanisms of USP28 in NSCLC.
Materials and methods: Immunoblotting analysis was used to detect relative proteins’ expression. Luciferase assay was performed to explore the activation of signal transducer and activator of transcription 3 (STAT3). Immunoprecipitation was performed to assess whether USP28 interacted with STAT3 or deubiquitinated STAT3. Quantitative real-time PCR was performed to evaluate the relative mRNA levels of STAT3 and USP28. Cycloheximide chase assay was carried out to examine whether USP28 affected the half-life of STAT3 protein. Cell Counting Kit-8 assay and xenograft model were used to assess whether USP28 regulated NSCLC cell growth.
Results: In this study, the deubiquitinating enzyme USP28 was found to mediate STAT3 signaling in NSCLC cells. USP28 interacted with STAT3, and increased the stability of STAT3 by inducing its deubiquitination. Further studies showed that USP28 was upregulated in both the primary tissues and cell lines of NSCLC. The Kaplan–Meier plotter also indicated that USP28 predicted a poor prognosis of NSCLC patients. Moreover, knockdown of USP28 inhibited cell growth of NSCLC cells in vitro and delayed NSCLC tumor growth in vivo.
Conclusion: These results demonstrated that USP28 was functional in NSCLC cells, and promoted NSCLC cell growth by inducing STAT3 signaling. This suggests that USP28 could be a novel target for NSCLC therapy.
Keywords: deubiquitinating enzyme, USP28, non-small-cell lung cancer, STAT3, deubiquitination
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