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Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells

  • Authors:
    • Sandra Cotino‑Nájera
    • Enrique García‑Villa
    • Samantha Cruz‑Rosales
    • Patricio Gariglio
    • José Díaz‑Chávez
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    Affiliations: Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of The National Polytechnic Institute, Mexico City 07360, Mexico, Biomedical Cancer Research Unit, Biomedical Research Institute, National Autonomous University of Mexico/National Cancer Institute, Mexico City 14080, Mexico
    Copyright: © Cotino‑Nájera et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 577
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    Published online on: September 30, 2024
       https://doi.org/10.3892/ol.2024.14710
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Abstract

Lin28A is an oncoprotein overexpressed in several cancer types such as testicular, ovarian, colon, breast and lung cancers. As a pluripotency factor that promotes tumorigenesis, Lin28A is associated with more undifferentiated and aggressive tumors phenotypes. Moreover, Lin28A is a highly stable protein that is difficult to downregulate. The compound resveratrol (RSV) has anticancer effects. The present study aimed to elucidate the mechanisms underlying the downregulation of Lin28A protein expression by RSV in the NCCIT cell line. NCCIT cells were treated with different concentrations of RSV to investigate its effects on Lin28A expression. The mRNA expression levels of Lin28A and ubiquitin‑specific protease 28 (USP28) were assessed using reverse transcription‑quantitative PCR. Western blot analysis was employed to evaluate the protein levels of Lin28A, USP28 and phosphorylated Lin28A. In addition, in some experiments, cells were treated with a MAPK/ERK pathway inhibitor, and other experiments involved transfecting cells with small interfering RNAs targeting USP28. The results demonstrated that RSV significantly reduced Lin28A expression by destabilizing the protein; this effect was mediated by the ability of RSV to suppress the expression of USP28, a deubiquitinase that normally protects Lin28A from ubiquitination and degradation. Additionally, RSV inhibited phosphorylation of Lin28A via the MAPK/ERK pathway; this phosphorylation event has previously been shown to enhance the stability of Lin28A by increasing its half‑life. This resulted in Lin28A degradation through the proteasomal pathway in NCCIT cells. The results provide further evidence of the anticancer activity of RSV, and identified Lin28A and USP28 as promising therapeutic targets. As a stable oncoprotein, downregulating Lin28A expression is challenging. However, the present study demonstrated that RSV can overcome this hurdle by inhibiting USP28 expression and MAPK/ERK signaling to promote Lin28A degradation. Furthermore, elucidating these mechanisms provides avenues for developing targeted cancer therapies.
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Spandidos Publications style
Cotino‑Nájera S, García‑Villa E, Cruz‑Rosales S, Gariglio P and Díaz‑Chávez J: Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells. Oncol Lett 28: 577, 2024.
APA
Cotino‑Nájera, S., García‑Villa, E., Cruz‑Rosales, S., Gariglio, P., & Díaz‑Chávez, J. (2024). Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells. Oncology Letters, 28, 577. https://doi.org/10.3892/ol.2024.14710
MLA
Cotino‑Nájera, S., García‑Villa, E., Cruz‑Rosales, S., Gariglio, P., Díaz‑Chávez, J."Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells". Oncology Letters 28.6 (2024): 577.
Chicago
Cotino‑Nájera, S., García‑Villa, E., Cruz‑Rosales, S., Gariglio, P., Díaz‑Chávez, J."Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells". Oncology Letters 28, no. 6 (2024): 577. https://doi.org/10.3892/ol.2024.14710
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Spandidos Publications style
Cotino‑Nájera S, García‑Villa E, Cruz‑Rosales S, Gariglio P and Díaz‑Chávez J: Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells. Oncol Lett 28: 577, 2024.
APA
Cotino‑Nájera, S., García‑Villa, E., Cruz‑Rosales, S., Gariglio, P., & Díaz‑Chávez, J. (2024). Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells. Oncology Letters, 28, 577. https://doi.org/10.3892/ol.2024.14710
MLA
Cotino‑Nájera, S., García‑Villa, E., Cruz‑Rosales, S., Gariglio, P., Díaz‑Chávez, J."Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells". Oncology Letters 28.6 (2024): 577.
Chicago
Cotino‑Nájera, S., García‑Villa, E., Cruz‑Rosales, S., Gariglio, P., Díaz‑Chávez, J."Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells". Oncology Letters 28, no. 6 (2024): 577. https://doi.org/10.3892/ol.2024.14710
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