Evidence map›Paper›PMID 23503458›Full record

ArticleOncogene2014

Downregulation of serine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells.

K Kurokawa, Y Akaike, K Masuda, Y Kuwano, K Nishida, N Yamagishi, K Kajita, T Tanahashi, K Rokutan

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. HIPK2 in the physiology of nervous system and its implications in neurological disorders.Biochimica et biophysica acta. Molecular cell research · 2023
    Review
  15. Article
  16. Review
  17. Article
  18. Oncogenic SRSF3 in health and diseases.International journal of biological sciences · 2023
    Review
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

K KurokawaDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Y AkaikeDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
K MasudaDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Y KuwanoDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
K NishidaDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
N YamagishiDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
K KajitaDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
T TanahashiDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
K RokutanDepartment of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Tokushima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Serine/arginine-rich splicing factor 3 (SRSF3) likely has wide-ranging roles in gene expression and facilitation of tumor cell growth. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116) in association with altered expression of 833 genes. Pathway analysis revealed 'G1/S Checkpoint Regulation' as the most highly enriched category in the affected genes. SRSF3 knockdown did not induce p53 or stimulate phosphorylation of p53 or histone H2A.X in wild-type HCT116 cells. Furthermore, the knockdown induced G1 arrest in p53-null HCT116 cells, suggesting that p53-dependent DNA damage responses did not mediate the G1 arrest. Real-time reverse transcription-polymerase chain reaction and western blotting confirmed that SRSF3 knockdown reduced mRNA and protein levels of cyclins (D1, D3 and E1), E2F1 and E2F7. The decreased expression of cyclin D and E2F1 likely impaired the G1-to-S-phase progression. Consequently, retinoblastoma protein remained hypophosphorylated in SRSF3 knockdown cells. The knockdown also induced apoptosis in association with reduction of BCL2 protein levels. We also found that SRSF3 knockdown facilitated skipping of 81 5'-nucleotides (27 amino acids) from exon 8 of homeodomain-interacting protein kinase-2 (HIPK2) and produced a HIPK2 Δe8 isoform. Full-length HIPK2 (HIPK2 FL) is constantly degraded through association with an E3 ubiquitin ligase (Siah-1), whereas HIPK2 Δe8, lacking the 27 amino acids, lost Siah-1-binding ability and became resistant to proteasome digestion. Interestingly, selective knockdown of HIPK2 FL induced apoptosis in various colon cancer cells expressing wild-type or mutated p53. Thus, these findings disclose an important role of SRSF3 in the regulation of the G1-to-S-phase progression and alternative splicing of HIPK2 in tumor growth.

Indexed as

Down-RegulationG1 PhaseAlternative SplicingApoptosisColonic NeoplasmsHumansRNA-Binding ProteinsSerine-Arginine Splicing FactorsRNA-Binding ProteinsSerine-Arginine Splicing FactorsSRSF3 protein, human

Identifiers

PMID23503458
OpenAlexW2090333731

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.