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Splicing factor 2/alternative splicing factor contributes to extracellular signal‑regulated kinase activation in hepatocellular carcinoma cells.

Abstract
The splicing factor is important in cancer development, modulation numerous tumor suppressors and oncogenes, and regulation of multiple signaling pathways. Splicing factor 2/alternative splicing factor (SF2/ASF) is a proto‑oncogene, which has been implicated in the development of hepatocellular carcinoma. However, the underlying molecular mechanism remains to be elucidated. In the present study, it was identified that SF2 knockdown had no effect on tumor necrosis factor (TNF)‑α‑induced activation of the c‑Jun N‑terminal protein kinase (JNK) pathway, the p38 pathway, or the IKK pathway in hepatoma cell lines. However, SF2 knockdown led to reduced levels of basal ERK activation and TNF‑α‑induced ERK activation, without changing the protein levels of ERK. Consequently, SF2 knockdown marginally enhanced TNF‑α‑induced cell death. Furthermore, SF2 knockdown and blockade of ERK activation partially suppressed TNF‑α‑induced interleukin‑6 expression. As SF2 knockdown exhibited no role in basal Akt activation and serum‑induced Akt activation, it is unlikely that SF2 affects ERK activation through modulating the protein levels of certain growth factor receptors. In conclusion, the data suggest that SF2 contributes to the elevated levels of ERK activation in hepatocellular carcinoma cells through modulating key component(s) downstream of growth factor receptors and upstream of ERK.
AuthorsYawei Zhao, Ting Zhu, Xueying Zhang, Qingyang Wang, Jiyan Zhang, Wenbin Ji, Yuanfang Ma
JournalMolecular medicine reports (Mol Med Rep) Vol. 12 Issue 3 Pg. 3890-3894 (Sep 2015) ISSN: 1791-3004 [Electronic] Greece
PMID26018840 (Publication Type: Journal Article)
Chemical References
  • IL6 protein, human
  • Interleukin-6
  • SRSF1 protein, human
  • Tumor Necrosis Factor-alpha
  • Serine-Arginine Splicing Factors
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
Topics
  • Apoptosis
  • Carcinogenesis (metabolism)
  • Carcinoma, Hepatocellular (metabolism)
  • Cell Line, Tumor
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Humans
  • Interleukin-6 (metabolism)
  • Liver Neoplasms (metabolism)
  • MAP Kinase Signaling System
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Serine-Arginine Splicing Factors (physiology)
  • Tumor Necrosis Factor-alpha (pharmacology)

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