4.7 Article

SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer

Journal

JOURNAL OF TRANSLATIONAL MEDICINE
Volume 19, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12967-021-02954-8

Keywords

SRPK1; NF-kappa B activation; Colon cancer; Anti-apoptosis; Oxaliplatin resistance

Funding

  1. Natural Science Foundation of China [81872448, 81973646, 82003789]
  2. Science and Technology Bureau of Shenzhen City [JCYJ20180305163414905]
  3. Discipline Construction Funding of Shenzhen [2016-1452]
  4. SZU medical young scientists' program [71201-000001]
  5. SZU high-level construction projects
  6. SZU Top Ranking Project [86000000210]

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SRPK1 is overexpressed in colon cancer and correlated with clinical stage and TNM classifications. High levels of SRPK1 are associated with poor prognosis. Mechanistically, SRPK1 enhances the anti-apoptosis ability of colon cancer cells under oxaliplatin treatment by promoting NF-κB pathway activation.
Background: Colorectal cancer is the third most common diagnosis. Oxaliplatin is used as first-line treatment of colon cancer. However, oxaliplatin resistance greatly reduces its therapeutic effect. SRPK1 involves in pre-mRNA splicing and tumorigenesis. How SRPK1 mediates drug resistance in colon cancer is unknown. Methods: The expression of SRPK1 was analyzed in the TCGA and the CPTAC pan-cancer samples and detected in colon cancer cell lines and tissues by IHC and western blot. The MTT and TUNEL assay were used to verify the anti-apoptosis ability of colon cancer cell. The activation of NF-kappa B was determined by luciferase assay and qRT-PCR. AKT, IKK, I kappa B and their phosphorylation level were verified by western blot. Results: We found that SRPK1 expression was the second highest in TCGA and the CPTAC pan-cancer samples. The mRNA and protein levels of SRPK1 were increased in tissues from patients with colon cancer. SRPK1 was associated with clinical stage and TNM classifications in 148 cases of colon cancer patients. High SRPK1 levels correlated with poor prognosis (p < 0.001). SRPK1 overexpression enhanced the anti-apoptosis ability of colon cancer cells, whereas SRPK1 silencing had the opposite effect under oxaliplatin treatment. Mechanistically, SRPK1 enhances IKK kinase and I kappa B phosphorylation to promote NF-kappa B nuclear translocation to confer oxaliplatin resistance. Conclusions: Our findings suggest that SRPK1 participates in colon cancer progression and enhances the anti-apoptosis capacity to induce drug resistance in colon cancer cells via NF-kappa B pathway activation, and thus might be a potential pharmaceutically target for colon cancer treatment.

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