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The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells

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Abstract

Background

Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling.

Methods and results

Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase.

Conclusions

Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

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Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Funding

The present study was supported by the grant from the Adiyaman University (Grand number: SHMYOMAP/2021-0001).

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Authors and Affiliations

  1. Department of Medical Services and Techniques, Vocational School of Health Services, Adiyaman University, Adiyaman, Turkey

    Esra Bozgeyik

  2. Department of Medical Genetics, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

    Haydar Bagis

  3. Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

    Ibrahim Bozgeyik

  4. Department of Physiology, Gulhane Medical Faculty, Health Sciences University, Ankara, Turkey

    Sayad Kocahan

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  1. Esra Bozgeyik
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Contributions

Esra Bozgeyik: Conceptualization, Methodology, Writing - Original Draft, Supervision, Haydar Bagis: Conceptualization, Writing - Review & Editing, Ibrahim Bozgeyik: Methodology, Writing - Original Draft, Writing - Review & Editing, Sayad Kocahan: Writing - Review & Editing.

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Correspondence to Esra Bozgeyik.

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Bozgeyik, E., Bagis, H., Bozgeyik, I. et al. The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells. Mol Biol Rep 50, 5021–5028 (2023). https://doi.org/10.1007/s11033-023-08441-1

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