Downregulation of SRPK2 promotes cell cycle arrest though E2F1 in non-small cell lung cancer

  • Xin Li Department of Oncology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Shaoyu Yang Department of Oncology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Minna Zhang Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
  • Shuhuan Xie Department of Thoracic Surgery, First Affiliated Hospital of Medical College of Shantou University, China.
  • Zefeng Xie | ZefengXieshj@163.com Department of Thoracic Surgery, First Affiliated Hospital of Medical College of Shantou University, China.

Abstract

Serine-arginine protein kinase (SRPK) belongs to a class of cell cycle regulating kinases that can phosphorylate proteins containing serine/arginine-Rich (SR) regions. SR proteins are a family of RNA binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. However, little is known about their role in non-small cell lung cancer (NSCLC). In the present study, we found that serine-arginine protein kinase 2 (SRPK2) expression was upregulated in NSCLC tissues compared with adjacent normal tissues. Kaplan-Meier curve analyses showed that the overall survival time of NSCLC patients with high SRPK2 expression was shorter than those with low SRPK2 expression. Overexpression of SRPK2 promoted NSCLC cell proliferation and cell cycle arrest, while knockdown of SRPK2 inhibited proliferation and promoted cell cycle arrest in NSCLC cell lines. SRPK2 promoted the transcriptional regulation of E2F1 on downstream cell cycle related genes through phosphorylation of SC35. Xenograft model showed that SRPK2 promoted tumor growth in vivo. SRPK2 phosphorylated SC35 and phosphorylated SC35 activated E2F1 transcription of cyclin-related proteins, thereby promoting the cycle progression of NSCLC. Our findings demonstrated that SRPK2 may be a potential therapeutic target for NSCLC clinical therapy, which plays an important role in the progression of NSCLC. 

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Published
2019-12-11
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Original Papers
Ethics Approval
Ethics Committee of First Affiliated Hospital of Shantou University Medical College, Written informed consent: obtained
Keywords:
SRPK2, NSCLC, E2F1, cell cycle
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How to Cite
Li, X., Yang, S., Zhang, M., Xie, S., & Xie, Z. (2019). Downregulation of SRPK2 promotes cell cycle arrest though E2F1 in non-small cell lung cancer. European Journal of Histochemistry, 63(4). https://doi.org/10.4081/ejh.2019.3067