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Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Background

RBM3 is a key RNA-binding protein that has been implicated in various cellular processes, including cell proliferation and cell cycle regulation. However, its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood.

Aims

We aimed to investigate the expression levels of RNA-binding motif protein 3 (RBM3) in patients with cSCC and evaluate its effect on cell ability in cSCC and its underlying regulatory mechanisms.

Methods

The expression of RBM3 in cSCC tissues and A431 cells was determined immunohistochemistry and western blotting. Plenti-CMV-RBM3-Puro was used to overexpress RBM3. The effect of RBM3 on the proliferation ability of cSCC cells was evaluated using MTT and colony formation assay. Cell apoptosis and cell cycle were determined using flow cytometry, while the protein expressions of BAX, NF-κB, BCL2, CASPASE 3, CYCLIN B, CYCLIN E, CDK1, phosphorylated (P)-CDK1, CDK2, P-CDK2, ERK, P-ERK, P-AMPK, AKT, P-AKT, MDM2, and P53 were assessed using western blotting.

Results

RBM3 expression was significantly downregulated in cSCC tissues and A431 cells. RBM3 overexpression significantly inhibited the cell proliferation and colony formation ability of A431. Notably, RNA-seq results showed that the differentially expressed genes associated with RBM3 were primarily involved in the regulation of the cell cycle, oocyte meiosis, and P53 signaling pathway, as well as the modulation of the MAPK, AMPK, Hippo, mTOR, PI3K/AKT, Wnt, FoxO, and NF-κB signaling pathways. Additionally, our findings demonstrated that overexpression of RBM3 inhibited cell proliferation and induced cell cycle arrest of cSCC through modulation of the PI3K/AKT signaling pathway.

Conclusion

This study provides novel insights into the suppressive roles of RBM3 in cell proliferation and the cell cycle in cSCC and highlights its therapeutic potential for cSCC.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2024-01-01
2025-05-23

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References

  1. de JongE. LammertsM. GendersR. E. Bouwes BavinckJ. N. Update of advanced cutaneous squamous cell carcinoma.J. Eur. Acad. Dermatol. Venereol.202236Suppl 161010.1111/jdv.17728
     [Google Scholar]
  2. BroughamN.D.L. TanS.T. The incidence and risk factors of metastasis for cutaneous squamous cell carcinoma-implications on the T-classification system.J. Surg. Oncol.2014110787688210.1002/jso.2373125088537
     [Google Scholar]
  3. MaubecE. Update of the management of cutaneous squamous-cell carcinoma.Acta Derm. Venereol.202010011adv0014310.2340/00015555‑349832346744
     [Google Scholar]
  4. QueS.K.T. ZwaldF.O. SchmultsC.D. Cutaneous squamous cell carcinoma.J. Am. Acad. Dermatol.201878224926110.1016/j.jaad.2017.08.05829332705
     [Google Scholar]
  5. ZhuX. BührerC. WellmannS. Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold.Cell. Mol. Life Sci.201673203839385910.1007/s00018‑016‑2253‑727147467
     [Google Scholar]
  6. EhlénÕ. NodinB. RexhepajE. BrändstedtJ. UhlénM. Alvarado-KristenssonM. PonténF. BrennanD.J. JirströmK. RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer.Transl. Oncol.201144212IN110.1593/tlo.1110621804916
     [Google Scholar]
  7. SakuraiT. KashidaH. KomedaY. NagaiT. HagiwaraS. WatanabeT. KitanoM. NishidaN. FujitaJ. KudoM. Stress response protein RBM3 promotes the development of colitis-associated cancer.Inflamm. Bowel Dis.2017231576510.1097/MIB.000000000000096827930406
     [Google Scholar]
  8. ChenP. YueX. XiongH. LuX. JiZ. RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression.Int. J. Oncol.20195441387139710.3892/ijo.2019.469830720048
     [Google Scholar]
  9. MiaoX. ZhangN. Role of RBM3 in the regulation of cell proliferation in hepatocellular carcinoma.Exp. Mol. Pathol.202011710454610.1016/j.yexmp.2020.10454632976820
     [Google Scholar]
  10. SalomonssonA. MickeP. MattssonJ.S.M. La FleurL. IsakssonJ. JönssonM. NodinB. BotlingJ. UhlénM. JirströmK. StaafJ. PlanckM. BrunnströmH. Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer.Cancer Med.20209155609561910.1002/cam4.314932491279
     [Google Scholar]
  11. HjelmB. BrennanD.J. ZendehrokhN. EberhardJ. NodinB. GaberA. PonténF. JohannessonH. SmaragdiK. FrantzC. HoberS. JohnsonL.B. PåhlmanS. JirströmK. UhlenM. High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer.Proteomics Clin. Appl.2011511-1262463510.1002/prca.20110002021956899
     [Google Scholar]
  12. EhlénÅ. BrennanD.J. NodinB. O’ConnorD.P. EberhardJ. Alvarado-KristenssonM. JeffreyI.B. ManjerJ. BrändstedtJ. UhlénM. PonténF. JirströmK. Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer.J. Transl. Med.2010817810.1186/1479‑5876‑8‑7820727170
     [Google Scholar]
  13. JonssonL. GaberA. UlmertD. UhlénM. BjartellA. JirströmK. High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression.Diagn. Pathol.2011619110.1186/1746‑1596‑6‑9121955582
     [Google Scholar]
  14. FengJ. PanW. YangX. LongF. ZhouJ. LiaoY. WangM. RBM3 increases cell survival but disrupts tight junction of microvascular endothelial cells in acute lung injury.J. Surg. Res.202126122623510.1016/j.jss.2020.12.04133460967
     [Google Scholar]
  15. WangP. WangC. LiuC. Antitumor effects of dioscin in A431 cells via adjusting ATM/p53-mediated cell apoptosis, DNA damage and migration.Oncol. Lett.20202115910.3892/ol.2020.1232133281970
     [Google Scholar]
  16. ChuF. XuX. ZhangY. CaiH. PengJ. LiY. ZhangH. LiuH. ChenX. LIM-domain binding protein 2 was down-regulated by miRNA-96-5p inhibited the proliferation, invasion and metastasis of lung cancer H1299 cells.Clinics20237810014510.1016/j.clinsp.2022.10014536473369
     [Google Scholar]
  17. LiP. FeiH. WangL. XuH. ZhangH. ZhengL. PDCD5 regulates cell proliferation, cell cycle progression and apoptosis.Oncol. Lett.201815111771183[https://doi.org/10.3892/ol.2017.7401]. [ PMID: 29403562].29403562
     [Google Scholar]
  18. GuH. LiL. CuiC. ZhaoZ. SongG. Overexpression of let-7a increases neurotoxicity in a PC12 cell model of Alzheimer’s disease via regulating autophagy.Exp. Ther. Med.20171443688369810.3892/etm.2017.497729042965
     [Google Scholar]
  19. JaminS.P. HikmetF. MathieuR. JégouB. LindskogC. ChalmelF. PrimigM. Combined RNA/tissue profiling identifies novel Cancer/testis genes.Mol. Oncol.202115113003302310.1002/1878‑0261.1290033426787
     [Google Scholar]
  20. Corchado-CobosR. García-SanchaN. González-SarmientoR. Pérez-LosadaJ. CañuetoJ. Cutaneous squamous cell carcinoma: From biology to therapy.Int. J. Mol. Sci.2020218295610.3390/ijms2108295632331425
     [Google Scholar]
  21. ChangM.S. AzinM. DemehriS. Cutaneous squamous cell carcinoma: The frontier of cancer immunoprevention.Annu. Rev. Pathol.202217110111910.1146/annurev‑pathol‑042320‑12005635073167
     [Google Scholar]
  22. KimJ.Y.S. KozlowJ.H. MittalB. MoyerJ. OleneckiT. RodgersP. AlamM. ArmstrongA. BaumC. BordeauxJ.S. BrownM. BusamK.J. EisenD.B. IyengarV. LoberC. MargolisD.J. MessinaJ. MillerA. MillerS. MostowE. MowadC. NehalK. Schmitt-BurrK. SekulicA. StorrsP. TengJ. YuS. HuangC. BoyerK. BegolkaW.S. BichakjianC. Work Group Invited Reviewers Guidelines of care for the management of cutaneous squamous cell carcinoma.J. Am. Acad. Dermatol.201878356057810.1016/j.jaad.2017.10.00729331386
     [Google Scholar]
  23. HedbergM.L. BerryC.T. MoshiriA.S. XiangY. YehC.J. AttilasoyC. CapellB.C. SeykoraJ.T. Molecular mechanisms of cutaneous squamous cell carcinoma.Int. J. Mol. Sci.2022237347810.3390/ijms2307347835408839
     [Google Scholar]
  24. HuY. LiuY. QuanX. FanW. XuB. LiS. RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia.J. Cell. Physiol.2022237103788380210.1002/jcp.3085235926117
     [Google Scholar]
  25. PerettiD. BastideA. RadfordH. VerityN. MolloyC. MartinM.G. MorenoJ.A. SteinertJ.R. SmithT. DinsdaleD. WillisA.E. MallucciG.R. RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration.Nature2015518753823623910.1038/nature1414225607368
     [Google Scholar]
  26. LongF. HuL. ChenY. DuanX. XieK. FengJ. WangM. RBM3 is associated with acute lung injury in septic mice and patients via the NF-κB/NLRP3 pathway.Inflamm. Res.202372473174410.1007/s00011‑023‑01705‑336781430
     [Google Scholar]
  27. Van PeltD.W. ConfidesA.L. JudgeA.R. VanderklishP.W. Dupont-VersteegdenE.E. Cold shock protein RBM3 attenuates atrophy and induces hypertrophy in skeletal muscle.J. Muscle Res. Cell Motil.2018391-2354010.1007/s10974‑018‑9496‑x30051360
     [Google Scholar]
  28. WongJ.J.L. AuA.Y.M. GaoD. PinelloN. KwokC.T. ThoengA. LauK.A. GordonJ.E.A. SchmitzU. FengY. NguyenT.V. MiddletonR. BaileyC.G. HolstJ. RaskoJ.E.J. RitchieW. RBM3 regulates temperature sensitive miR-142–5p and miR-143 (thermomiRs), which target immune genes and control fever.Nucleic Acids Res.20164462888289710.1093/nar/gkw04126825461
     [Google Scholar]
  29. ZhangS. LvC. NiuY. LiC. LiX. ShangY. ZhangY. ZhangY. ZhangY. ZengY. RBM3 suppresses stemness remodeling of prostate cancer in bone microenvironment by modulating N6-methyladenosine on CTNNB1 mRNA.Cell Death Dis.20231429110.1038/s41419‑023‑05627‑036750551
     [Google Scholar]
  30. ZhouR.B. LuX.L. ZhangC.Y. YinD.C. RNA binding motif protein 3: A potential biomarker in cancer and therapeutic target in neuroprotection.Oncotarget2017813222352225010.18632/oncotarget.1475528118608
     [Google Scholar]
  31. JonssonL. BergmanJ. NodinB. ManjerJ. PonténF. UhlénM. JirströmK. Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: An analysis of 215 cases from the Malmö Diet and Cancer Study.J. Transl. Med.20119111410.1186/1479‑5876‑9‑11421777469
     [Google Scholar]
  32. ShalhoutS.Z. EmerickK.S. KaufmanH.L. MillerD.M. Immunotherapy for non-melanoma skin cancer.Curr. Oncol. Rep.2021231112510.1007/s11912‑021‑01120‑z34448958
     [Google Scholar]
  33. Al-AstalH.I. MassadM. AlMatarM. EkalH. Cellular functions of RNA-binding motif protein 3 (RBM3): Clues in hypothermia, cancer biology and apoptosis.Protein Pept. Lett.201623982883510.2174/092986652366616062809034027364162
     [Google Scholar]
  34. KangS.H. ChoJ. JeongH. KwonS.Y. High RNA-binding motif protein 3 expression is associated with improved clinical outcomes in invasive breast cancer.J. Breast Cancer201821328829610.4048/jbc.2018.21.e3430275857
     [Google Scholar]
  35. JögiA. BrennanD.J. RydénL. MagnussonK. FernöM. StålO. BorgquistS. UhlenM. LandbergG. PåhlmanS. PonténF. JirströmK. Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer.Mod. Pathol.200922121564157410.1038/modpathol.2009.12419734850
     [Google Scholar]
  36. FlorianovaL. XuB. TraboulsiS. ElmansiH. TanguayS. AprikianA. KassoufW. BrimoF. Evaluation of RNA-binding motif protein 3 expression in urothelial carcinoma of the bladder: An immunohistochemical study.World J. Surg. Oncol.201513131710.1186/s12957‑015‑0730‑326577765
     [Google Scholar]
  37. JangH.H. LeeH.N. KimS.Y. HongS. LeeW.S. Expression of RNA-binding motif protein 3 (RBM3) and cold-inducible RNA-binding protein (CIRP) is associated with improved clinical outcome in patients with colon cancer.Anticancer Res.20173741779178510.21873/anticanres.1151128373441
     [Google Scholar]
  38. WahlinS. BomanK. MoranB. NodinB. GallagherW.M. KarneviE. JirströmK. Pre-clinical and clinical studies on the role of RBM3 in muscle-invasive bladder cancer: Longitudinal expression, transcriptome-level effects and modulation of chemosensitivity.BMC Cancer202222113110.1186/s12885‑021‑09168‑735109796
     [Google Scholar]
  39. ZengY. WodzenskiD. GaoD. ShiraishiT. TeradaN. LiY. Vander GriendD.J. LuoJ. KongC. GetzenbergR.H. KulkarniP. Stress-response protein RBM3 attenuates the stem-like properties of prostate cancer cells by interfering with CD44 variant splicing.Cancer Res.201373134123413310.1158/0008‑5472.CAN‑12‑134323667174
     [Google Scholar]
  40. NodinB. FridbergM. JonssonL. BergmanJ. UhlénM. JirströmK. High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma.Diagn. Pathol.2012718210.1186/1746‑1596‑7‑8222805320
     [Google Scholar]
  41. SurebanS.M. RamalingamS. NatarajanG. MayR. SubramaniamD. BishnupuriK.S. MorrisonA.R. DieckgraefeB.K. BrackettD.J. PostierR.G. HouchenC.W. AnantS. Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe.Oncogene200827334544455610.1038/onc.2008.9718427544
     [Google Scholar]
  42. DongW. DaiZ. LiuF. GuoX. GeC. DingJ. LiuH. YangF. The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production.EBioMedicine20194515516710.1016/j.ebiom.2019.06.03031235426
     [Google Scholar]
  43. WangS. ChenX. QiaoT. Long non-coding RNA MIR4435‑2HG promotes the progression of head and neck squamous cell carcinoma by regulating the miR-383-5p/RBM3 axis.Oncol. Rep.20214569910.3892/or.2021.805033846802
     [Google Scholar]
  44. LinJ.Q. KhuperkarD. PavlouS. MakarchukS. PatikasN. LeeF.C.Y. ZbieglyJ.M. KangJ. FieldS.F. BaileyD.M.D. FreemanJ.L. UleJ. MetzakopianE. RueppM.D. MallucciG.R. HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion.EMBO J.20234214e11316810.15252/embj.202211316837248947
     [Google Scholar]
  45. XuY. WuW. HanQ. WangY. LiC. ZhangP. XuH. Post-translational modification control of RNA-binding protein hnRNPK function.Open Biol.20199318023910.1098/rsob.18023930836866
     [Google Scholar]
  46. SinghH. ChopraH. SinghI. MohantoS. AhmedM.G. GhumraS. SeelanA. SurvaseM. KumarA. MishraA. MishraA.K. KamalM.A. Molecular targeted therapies for cutaneous squamous cell carcinoma: Recent developments and clinical implications.EXCLI J.20242330033410.1098/rsob.18023938655092
     [Google Scholar]
  47. RatushnyV. GoberM.D. HickR. RidkyT.W. SeykoraJ.T. From keratinocyte to cancer: The pathogenesis and modeling of cutaneous squamous cell carcinoma.J. Clin. Invest.2012122246447210.1172/JCI5741522293185
     [Google Scholar]
  48. Di NardoL. PellegriniC. Di StefaniA. Del RegnoL. SollenaP. PiccerilloA. LongoC. GarbeC. FargnoliM.C. PerisK. Molecular genetics of cutaneous squamous cell carcinoma: perspective for treatment strategies.J. Eur. Acad. Dermatol. Venereol.202034593294110.1111/jdv.1609831747091
     [Google Scholar]
  49. GongZ. ZhangY. JiangY. ChenP. JiJ. LncRNA NEAT1 targets miR-342-3p/CUL4B to inhibit the proliferation of cutaneous squamous cell carcinoma cells.J. Oncol.202220221810.1155/2022/814512935909905
     [Google Scholar]
  50. CiC. WuC. LyuD. ChangX. HeC. LiuW. ChenL. DingW. Downregulation of kynureninase restrains cutaneous squamous cell carcinoma proliferation and represses the PI3K/AKT pathway.Clin. Exp. Dermatol.202045219420110.1111/ced.1407231419330
     [Google Scholar]
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RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway
Curr Mol Pharmacol 17, e18761429323760 (2024); https://doi.org/10.2174/0118761429323760240712050006
/content/journals/cmp/10.2174/0118761429323760240712050006
/content/journals/cmp/10.2174/0118761429323760240712050006
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  • Article Type:     Research Article
Keyword(s): Cell cycle; Cutaneous squamous cell carcinoma; PI3K/AKT signaling pathway; Proliferation; RBM3

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