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2000
Volume 28, Issue 14
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

The aim of this study is to explore the mechanism of HRAS and HSPB1 in ferroptosis. Primary liver cancer is the third leading cause of tumor death worldwide. Hepatocellular carcinoma (HCC) constitutes 75%-85% of cases of primary liver cancer. HRAS and HSPB1 co-express in multiple cells and participate in tumor progression regulation. However, their expression regulation and role in HCC have not been reported.

Methods

We investigated the effects of HRAS and HSPB1 on ferroptosis in experiments. Here, the role and mechanism of HRAS and HSPB1 on ferroptosis were investigated by transfecting the specific siRNA or overexpressing plasmids in HCC cells.

Results

Bioinformatics analysis proved that HRAS and HSPB1 were highly expressed in HCC tissues and associated with poor prognosis of patients with HCC. , HRAS overexpression reduced the level of intracellular iron, ROS, and MDA production in HCC cells. Mechanistically, HRAS increased GPX4 expression and decreased the levels of ACSL4 and P53. HRAS also increased HSPB1 expression, and HRAS knockdown downregulated HSPB1 levels in HCC cells. Importantly, overexpression of HSPB1 reversed HRAS-increased concentration of iron, MDA, and ROS and eliminated HRAS-induced ferroptosis. Moreover, HRAS enhanced the proliferation and invasion by targeting HSPB1.

Conclusion

The regulation of HSPB1 by HRAS enhanced the resistance of HCC cells to ferroptosis. HRAS promoted proliferation and invasion by upregulating HSPB1. This research provides a new potential strategy for HCC treatment.

© 2025 Bentham Science Publishers
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2024-07-22
2025-11-03

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References

  1. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  2. AdenijiN. DhanasekaranR. Genomic Landscape of HCC.Curr. Hepatol. Rep.202019444846110.1007/s11901‑020‑00553‑7 33816052
     [Google Scholar]
  3. TangD. ChenX. KangR. KroemerG. Ferroptosis: molecular mechanisms and health implications.Cell Res.202131210712510.1038/s41422‑020‑00441‑1 33268902
     [Google Scholar]
  4. ChenX. LiJ. KangR. KlionskyD.J. TangD. Ferroptosis: machinery and regulation.Autophagy20211792054208110.1080/15548627.2020.1810918 32804006
     [Google Scholar]
  5. MaT. DuJ. ZhangY. WangY. WangB. ZhangT. GPX4-independent ferroptosis—a new strategy in disease’s therapy.Cell Death Discov.20228143410.1038/s41420‑022‑01212‑0 36309489
     [Google Scholar]
  6. BattagliaA.M. ChirilloR. AversaI. SaccoA. CostanzoF. BiamonteF. Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death.Cells202096150510.3390/cells9061505 32575749
     [Google Scholar]
  7. ZhangC. LiuX. JinS. ChenY. GuoR. Ferroptosis in cancer therapy: A novel approach to reversing drug resistance.Mol. Cancer20222114710.1186/s12943‑022‑01530‑y 35151318
     [Google Scholar]
  8. LiuY. ZhouL. XuY. LiK. ZhaoY. QiaoH. XuQ. ZhaoJ. Heat Shock Proteins and Ferroptosis.Front. Cell Dev. Biol.20221086463510.3389/fcell.2022.864635 35478955
     [Google Scholar]
  9. ShanQ. MaF. WeiJ. LiH. MaH. SunP. Physiological Functions of Heat Shock Proteins.Curr. Protein Pept. Sci.202021875176010.2174/1389203720666191111113726 31713482
     [Google Scholar]
  10. SunX. OuZ. XieM. KangR. FanY. NiuX. WangH. CaoL. TangD. HSPB1 as a novel regulator of ferroptotic cancer cell death.Oncogene201534455617562510.1038/onc.2015.32 25728673
     [Google Scholar]
  11. LiangY. WangY. ZhangY. YeF. LuoD. LiY. JinY. HanD. WangZ. ChenB. ZhaoW. WangL. ChenX. MaT. KongX. YangQ. HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer.Cell Death Dis.202314743410.1038/s41419‑023‑05972‑0 37454220
     [Google Scholar]
  12. FeiZ. LijuanY. JingZ. XiY. YuefenP. ShuwenH. Molecular characteristics associated with ferroptosis in hepatocellular carcinoma progression.Hum. Cell202134117718610.1007/s13577‑020‑00431‑w 32936424
     [Google Scholar]
  13. TangZ. LiC. KangB. GaoG. LiC. ZhangZ. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses.Nucleic Acids Res.201745W1W98W10210.1093/nar/gkx247 28407145
     [Google Scholar]
  14. BoikovaA. BywaterM.J. Quaife-RyanG.A. StraubeJ. ThompsonL. AscanelliC. LittlewoodT.D. EvanG.I. HudsonJ.E. WilsonC.H. HRas and Myc synergistically induce cell cycle progression and apoptosis of murine cardiomyocytes.Front. Cardiovasc. Med.2022994828110.3389/fcvm.2022.948281 36337898
     [Google Scholar]
  15. WanX. LiuR. LiZ. The Prognostic Value of HRAS mRNA Expression in Cutaneous Melanoma.BioMed Res. Int.2017201711210.1155/2017/5356737 29349077
     [Google Scholar]
  16. KimD. HerdeisL. RudolphD. ZhaoY. BöttcherJ. VidesA. Ayala-SantosC.I. PourfarjamY. Cuevas-NavarroA. XueJ.Y. MantoulidisA. BrökerJ. WunbergT. SchaafO. PopowJ. WolkerstorferB. KropatschK.G. QuR. de StanchinaE. SangB. LiC. McConnellD.B. KrautN. LitoP. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth.Nature2023619796816016610.1038/s41586‑023‑06123‑3 37258666
     [Google Scholar]
  17. HomamiA. Ataei KachoeiZ. AsgarieM. GhaziF. Analysis of FGFR3 and HRAS genes in patients with bladder cancer.Med. J. Islam. Repub. Iran20203410810.47176/mjiri.34.108 33316010
     [Google Scholar]
  18. DesiletsA. HoA.L. Targeting HRAS in Head and Neck Cancer.Cancer J.202228536336810.1097/PPO.0000000000000616 36165724
     [Google Scholar]
  19. NakaguroM. TadaY. FaquinW.C. SadowP.M. WirthL.J. NagaoT. Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment.Cancer Cytopathol.20201281069370310.1002/cncy.22288 32421944
     [Google Scholar]
  20. LiS. WuL. ZhangH. LiuX. WangZ. DongB. CaoG. GINS1 Induced Sorafenib Resistance by Promoting Cancer Stem Properties in Human Hepatocellular Cancer Cells.Front. Cell Dev. Biol.2021971189410.3389/fcell.2021.711894 34414190
     [Google Scholar]
  21. LiuY. XinB. YamamotoM. GotoM. OoshioT. KamikokuraY. TanakaH. MengL. OkadaY. MizukamiY. NishikawaY. Generation of combined hepatocellular‐cholangiocarcinoma through transdifferentiation and dedifferentiation in p53‐knockout mice.Cancer Sci.202111283111312410.1111/cas.14996 34051011
     [Google Scholar]
  22. KamiokaH. YogosawaS. OikawaT. AizawaD. UedaK. SaekiC. HarukiK. ShimodaM. IkegamiT. NishikawaY. SarutaM. YoshidaK. Dyrk2 gene transfer suppresses hepatocarcinogenesis by promoting the degradation of Myc and Hras.JHEP Reports20235710075910.1016/j.jhepr.2023.100759 37333975
     [Google Scholar]
  23. ZouJ. QinW. Comprehensive analysis of the cancer driver genes constructs a seven-gene signature for prediction of survival and tumor immunity in hepatocellular carcinoma.Front. Genet.20221393794810.3389/fgene.2022.937948 36017503
     [Google Scholar]
  24. SunH. QianX. YangW. ZhouW. ZhouC. LiuS. ShiH. TianW. Novel prognostic signature based on HRAS, MAPK3 and TFRC identified to be associated with ferroptosis and the immune microenvironment in hepatocellular carcinoma.Am. J. Transl. Res.2022141069246940 36398204
     [Google Scholar]
  25. ZhangL. ChenX. GuoX. ShenH. QiuD. JinW. HouD. Comprehensive analysis of cell death genes in hepatocellular carcinoma based on multi-omics data.Adv. Clin. Exp. Med.202332223324410.17219/acem/152737 36753369
     [Google Scholar]
  26. DuX. QiZ. XuJ. GuoM. ZhangX. YuZ. CaoX. XiaJ. Loss of GABARAPL1 confers ferroptosis resistance to cancer stem‐like cells in hepatocellular carcinoma.Mol. Oncol.202216203703371910.1002/1878‑0261.13305 36062307
     [Google Scholar]
  27. XieY. KangR. KlionskyD.J. TangD. GPX4 in cell death, autophagy, and disease.Autophagy202319102621263810.1080/15548627.2023.2218764 37272058
     [Google Scholar]
  28. DollS. PronethB. TyurinaY.Y. PanziliusE. KobayashiS. IngoldI. IrmlerM. BeckersJ. AichlerM. WalchA. ProkischH. TrümbachD. MaoG. QuF. BayirH. FüllekrugJ. ScheelC.H. WurstW. SchickJ.A. KaganV.E. AngeliJ.P.F. ConradM. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition.Nat. Chem. Biol.2017131919810.1038/nchembio.2239 27842070
     [Google Scholar]
  29. HuJ. CaoJ. TopatanaW. JuengpanichS. LiS. ZhangB. ShenJ. CaiL. CaiX. ChenM. Targeting mutant p53 for cancer therapy: direct and indirect strategies.J. Hematol. Oncol.202114115710.1186/s13045‑021‑01169‑0 34583722
     [Google Scholar]
  30. JiangL. KonN. LiT. WangS.J. SuT. HibshooshH. BaerR. GuW. Ferroptosis as a p53-mediated activity during tumour suppression.Nature20155207545576210.1038/nature14344 25799988
     [Google Scholar]
  31. AmranN. Abdul-RahmanP.S. Differential proteome and functional analysis of NSCLC cell lines in response to Tualang honey treatment.J. Ethnopharmacol.202229311526410.1016/j.jep.2022.115264 35398242
     [Google Scholar]
  32. AryaA.K. SinghP. SaikiaU.N. SachdevaN. DahiyaD. BeheraA. RaoS.D. BhadadaS.K. Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.J. Endocrinol. Invest.202043224725310.1007/s40618‑019‑01098‑3 31535356
     [Google Scholar]
  33. HeredeaR.E. MelnicE. CirligeriuL.E. BerzavaP.L. StănciulescuM.C. PopoiuC.M. CimpeanA.M. VEGF Pathway Gene Expression Profile of Proliferating versus Involuting Infantile Hemangiomas: Preliminary Evidence and Review of the Literature.Children (Basel)20229690810.3390/children9060908 35740845
     [Google Scholar]
/content/journals/cchts/10.2174/0113862073306462240710174817
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HRAS Induces Ferroptosis through Upregulating HSPB1 in Hepatocellular Carcinoma
Comb Chem High Throughput Screen 28, 2502 (2025); https://doi.org/10.2174/0113862073306462240710174817
/content/journals/cchts/10.2174/0113862073306462240710174817
/content/journals/cchts/10.2174/0113862073306462240710174817
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  • Article Type:     Research Article
Keyword(s): ferroptosis; Hepatocellular carcinoma; HRAS and HSPB1; Ras family; ROS; transcription factor

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