Resveratrol affects ccRCC cell senescence and macrophage polarization by regulating the stability of CCNB1 by RBM15
Abstract
Aim: The present study sought to investigate the therapeutic effect of resveratrol on clear cell renal cell carcinoma. Materials & methods: Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to verify the cell proliferation. Transwell, real-time quantitative transcription PCR, western blot and β-galactosidase staining were used to verify the migration, macrophage polarization and senescence. The tumor inhibitory effect of resveratrol on clear cell renal cell carcinoma was verified in vivo. Results: This study confirmed that resveratrol could affect the stability of CCNB1 mRNA mediated by RBM15 and inhibit the cancer process by inhibiting the expression of EP300/CBP from the perspective of cell senescence. Conclusion: Resveratrol is able to treat clear cell renal cell carcinoma through RBM15-induced cell senescence.
Tweetable abstract
A recent study has shown that resveratrol RBM15 mRNA stability and suppressing cancer cell proliferation, offering a promising therapeutic approach for kidney cancer. #Resveratrol #Kidney Cancer
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Combined treatment with valproic acid and 5-Aza-2′-deoxycytidine synergistically inhibits human clear cell renal cell carcinoma growth and migration. Med. Sci. Monit. 24, 1034–1043 (2018).
- 2. Optimized combination of HDACI and TKI efficiently inhibits metabolic activity in renal cell carcinoma and overcomes sunitinib resistance. Cancers (Basel). 12(11), (2020).
- 3. CBX4 transcriptionally suppresses KLF6 via interaction with HDAC1 to exert oncogenic activities in clear cell renal cell carcinoma. EBioMedicine. 53, 102692 (2020).
- 4. . Efficacy and safety of HDACIs in the treatment of metastatic or unresectable renal cell carcinoma with a clear cell phenotype: a systematic review and meta-analysis. Medicine (Baltimore). 100(31), e26788 (2021).
- 5. Functions of N6-methyladenosine and its role in cancer. Mol. Cancer 18(1), 176 (2019).
- 6. Insights into N6-methyladenosine and programmed cell death in cancer. Mol. Cancer 21(1), 32 (2022).
- 7. N6-methyladenosine reader YTHDF1 promotes ARHGEF2 translation and RhoA signaling in colorectal cancer. Gastroenterology 162(4), 1183–1196 (2022).
- 8. . The potential role of RNA N6-methyladenosine in cancer progression. Mol. Cancer. 19(1), 88 (2020). • This research idea provides the basis.
- 9. Resveratrol for cancer therapy: challenges and future perspectives. Cancer Lett. 515, 63–72 (2021). •• This report provided significant guidance for drug selection in this study.
- 10. . Resveratrol and cancer: focus on in vivo evidence. Endocr. Relat. Cancer. 21(3), R209–225 (2014).
- 11. . Resveratrol and Prostate Cancer: The Power of Phytochemicals. Curr Med Chem. 28(24), 4845–4862 (2021).
- 12. . Mitochondrial metabolic reprogramming by SIRT3 regulation ameliorates drug resistance in renal cell carcinoma. PLOS ONE 17(6), e0269432 (2022).
- 13. . Health benefits of resveratrol administration. Acta Biochim. Pol. 66(1), 13–21 (2019).
- 14. Resveratrol as an anti-cancer agent: a review. Crit. Rev. Food Sci. Nutr. 58(9), 1428–1447 (2018).
- 15. METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer. Mol. Cancer. 18(1), 142 (2019).
- 16. Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11. Free Radic. Biol. Med. 184, 135–147 (2022). • This research idea provides the basis for this work.
- 17. Resveratrol drives cancer cell senescence via enhancing p38MAPK and DLC1 expressions. Food Funct. 13(6), 3283–3293 (2022).
- 18. Resveratrol induces DNA damage-mediated cancer cell senescence through the DLC1-DYRK1A-EGFR axis. Food Funct. 14(3), 1484–1497 (2023).
- 19. Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer. J. Cell Physiol. 234(1), 619–631 (2018).
- 20. Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression. Arch Toxicol. 94(10), 3433–3447 (2020).
- 21. Cellular senescence impact on immune cell fate and function. Aging Cell. 15(3), 400–406 (2016). • This study referred to the role of SASP in cell senescence and tumor progression.
- 22. . Overexpression of miR-15b promotes resistance to sunitinib in renal cell carcinoma. J. Cancer. 10(15), 3389–3396 (2019).
- 23. Pharmacological targeting of CBP/p300 drives a redox/autophagy axis leading to senescence-induced growth arrest in non-small cell lung cancer cells. Cancer Gene Ther.
doi: 10.1038/s41417-022-00524-8 (2022). - 24. The transcription factor ZBP-89 suppresses p16 expression through a histone modification mechanism to affect cell senescence. Febs J. 276(15), 4197–4206 (2009).
- 25. . Senescence and the SASP: many therapeutic avenues. Genes Dev. 34(23–24), 1565–1576 (2020).
- 26. . The senescence-associated secretory phenotype (SASP) in the challenging future of cancer therapy and age-related diseases. Biology (Basel). 9(12), (2020).
- 27. . Senescence in health and disease. Cell 169(6), 1000–1011 (2017).
- 28. Cellular senescence and cancer: Focusing on traditional Chinese medicine and natural products. Cell Prolif. 53(10), e12894 (2020).
- 29. Senescence and Cancer: Role of Nitric Oxide (NO) in SASP. Cancers (Basel). 12(5), (2020).
- 30. . Cellular senescence and the tumour microenvironment. Mol. Oncol. 16(18), 3333–3351 (2022).
- 31. . Senescent cells in cancer therapy: friends or foes? Trends Cancer 6(10), 838–857 (2020).
- 32. Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Theranostics 10(15), 6928–6945 (2020).
- 33. Carnitine palmitoyltransferase 1C regulates cancer cell senescence through mitochondria-associated metabolic reprograming. Cell Death Differ. 25(4), 735–748 (2018).
- 34. . Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9. PLOS ONE 14(7), e0219317 (2019).
- 35. . The effect of resveratrol on cellular senescence in normal and cancer cells: focusing on cancer and age-related diseases. Nutr Cancer 71(7), 1175–1180 (2019).
- 36. . Effect of resveratrol and pterostilbene on aging and longevity. Biofactors. 44(1), 69–82 (2018).
- 37. Mechanisms of aging and the preventive effects of resveratrol on age-related diseases. Molecules 25(20), (2020).
- 38. HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis. Aging (Albany NY). 11(18), 7473–7491 (2019).
- 39. MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma. Cell Death Dis. 12(7), 691 (2021).
- 40. CDK1, CCNB1, and CCNB2 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma. Med. Sci. Monit. 26, e925289 (2020).
- 41. Legumain-deficient macrophages promote senescence of tumor cells by sustaining JAK1/STAT1 activation. Cancer Lett. 472, 40–49 (2020).