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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

The gene encoding the splicing factor SF2/ASF is a proto-oncogene

Rotem Karni1, Elisa de Stanchina, Scott W Lowe

  • 1Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA.

Nature Structural & Molecular Biology
|February 21, 2007
PubMed

Insights

The splicing factor SF2/ASF, when overexpressed, acts as an oncoprotein driving cancer development by altering tumor suppressor and kinase splicing. Targeting SF2/ASF offers a potential cancer therapy strategy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Alternative splicing significantly impacts the expression of oncogenes and tumor suppressors.
  • The role of alternative splicing factors in cancer development remains an area of active investigation.

Purpose of the Study:

  • To investigate the involvement of splicing factors in cancer.
  • To determine if SF2/ASF functions as an oncoprotein and explore its therapeutic potential.

Main Methods:

  • Analysis of SF2/ASF expression in human tumors.
  • Cell transformation assays using rodent fibroblasts.
  • Investigation of SF2/ASF's control over alternative splicing of BIN1, MNK2, and S6K1.
  • In vitro and in vivo knockdown experiments.

Main Results:

  • SF2/ASF (Splicing Factor 2/Alternative Splicing) is upregulated in human tumors, partly due to SFRS1 gene amplification.
  • SF2/ASF overexpression transforms rodent fibroblasts into sarcoma-forming cells.
  • SF2/ASF regulates splicing of BIN1, MNK2, and S6K1, generating isoforms with altered functions.
  • Knockdown of SF2/ASF or S6K1 isoform 2 reverses oncogenic transformation.

Conclusions:

  • SF2/ASF functions as an oncoprotein by manipulating alternative splicing pathways.
  • SF2/ASF-driven oncogenesis involves specific isoforms of BIN1, MNK2, and S6K1.
  • SF2/ASF represents a promising therapeutic target for various cancers.

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