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2000
Volume 32, Issue 30
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X
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Abstract

Introduction

Osteosarcoma (OS) drug resistance often leads to a poor prognosis. Recent evidence suggests that long non-coding RNAs play a crucial role in regulating tumor drug resistance.

Methods

This study aims to investigate the involvement of lncRNA LAMTOR5-AS1 in OS. RNA-seq and qRT-PCR were performed, and the relationship between LAMTOR5-AS1, miR-34a-3p, SIRT1, and HNF4A was determined using Dual-luciferase reporter assays and RNA immunoprecipitation assays. Gain- and loss-of-function assays were measured using CCK-8, cell proliferation, and colony formation assays.

Results

The study found that the dysregulated LAMTOR5-AS1 acts as a competing endogenous RNA (ceRNA) and competitively protects the HNF4A mRNA 3’ UTR from miR-34a-3p. In addition, functional studies showed that HNF4A can physically interact with SIRT1 to synergistically inhibit osteosarcoma drug resistance. The study found that LAMTOR5-AS1 regulates drug resistance in osteosarcoma through the miR-34a-3p/HNF4A or miR-34a-3p/SIRT1/HNF4A axis.

Conclusion

These findings offer new insights into lncRNA-mediated drug resistance in cancer and may serve as potential biomarkers for cancer therapy.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. MooreD.D. LuuH.H. Osteosarcoma.Cancer Treat. Res.2014162659210.1007/978‑3‑319‑07323‑1_425070231
     [Google Scholar]
  2. LinkM.P. GoorinA.M. MiserA.W. GreenA.A. PrattC.B. BelascoJ.B. PritchardJ. MalpasJ.S. BakerA.R. KirkpatrickJ.A. AyalaA.G. ShusterJ.J. AbelsonH.T. SimoneJ.V. ViettiT.J. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity.N. Engl. J. Med.1986314251600160610.1056/NEJM1986061931425023520317
     [Google Scholar]
  3. HeH. NiJ. HuangJ. Molecular mechanisms of chemoresistance in osteosarcoma (Review).Oncol. Lett.2014751352136210.3892/ol.2014.193524765137
     [Google Scholar]
  4. ScocciantiC. VesinA. MartelG. OlivierM. BrambillaE. TimsitJ.F. TavecchioL. BrambillaC. FieldJ.K. HainautP. Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: The EUELC cohort.Eur. Respir. J.201240117718410.1183/09031936.0009731122267755
     [Google Scholar]
  5. JingC. MaoX. WangZ. SunK. MaR. WuJ. CaoH. Next-generation sequencing-based detection of EGFR, KRAS, BRAF, NRAS, PIK3CA, Her-2 and TP53 mutations in patients with non-small cell lung cancer.Mol. Med. Rep.20181822191219710.3892/mmr.2018.921029956783
     [Google Scholar]
  6. MogiA. KuwanoH. TP53 mutations in nonsmall cell lung cancer.J. Biomed. Biotechnol.201120111910.1155/2011/58392921331359
     [Google Scholar]
  7. PontingC.P. OliverP.L. ReikW. Evolution and functions of long noncoding RNAs.Cell2009136462964110.1016/j.cell.2009.02.00619239885
     [Google Scholar]
  8. LuW. ZhangH. NiuY. WuY. SunW. LiH. KongJ. DingK. ShenH.M. WuH. XiaD. WuY. Erratum to: Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p.Mol. Cancer201716114410.1186/s12943‑017‑0716‑628851432
     [Google Scholar]
  9. LuW. ZhangH. NiuY. WuY. SunW. LiH. KongJ. DingK. ShenH.M. WuH. XiaD. WuY. Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p.Mol. Cancer201716111810.1186/s12943‑017‑0685‑928697764
     [Google Scholar]
  10. ZhouS. YuL. XiongM. DaiG. LncRNA SNHG12 promotes tumorigenesis and metastasis in osteosarcoma by upregulating Notch2 by sponging miR-195-5p.Biochem. Biophys. Res. Commun.201849521822183210.1016/j.bbrc.2017.12.04729229388
     [Google Scholar]
  11. ZhouB. LiL. LiY. SunH. ZengC. Long noncoding RNA SNHG12 mediates doxorubicin resistance of osteosarcoma via miR-320a/MCL1 axis.Biomed. Pharmacother.2018106850857
     [Google Scholar]
  12. ChoS.W. XuJ. SunR. MumbachM.R. CarterA.C. ChenY.G. YostK.E. KimJ. HeJ. NevinsS.A. ChinS.F. CaldasC. LiuS.J. HorlbeckM.A. LimD.A. WeissmanJ.S. CurtisC. ChangH.Y. Promoter of lncRNA gene PVT1 Is a tumor-suppressor DNA boundary element.Cell2018173613981412.e2210.1016/j.cell.2018.03.06829731168
     [Google Scholar]
  13. TuliL. RessomH.W. LC-MS based detection of differential protein expression.J. Proteomics Bioinform.2009241643810.4172/jpb.100010220473349
     [Google Scholar]
  14. HuangZ. HuangS. WangQ. LiangL. NiS. WangL. ShengW. HeX. DuX. MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma.Cancer Res.20117172582258910.1158/0008‑5472.CAN‑10‑303221427358
     [Google Scholar]
  15. SangB. ZhangY.Y. GuoS.T. KongL.F. ChengQ. LiuG.Z. ThorneR.F. ZhangX.D. JinL. WuM. Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence.Proc. Natl. Acad. Sci. USA201811550E11661E1167010.1073/pnas.180595011530478051
     [Google Scholar]
  16. KangK.A. HyunJ.W. Oxidative stress, Nrf2, and epigenetic modification contribute to anticancer drug resistance.Toxicol. Res.20173311510.5487/TR.2017.33.1.00128133507
     [Google Scholar]
  17. PuY. TanY. ZangC. ZhaoF. CaiC. KongL. DengH. ChaoF. XiaR. XieM. GeF. PanY. CaiS. HuangD. LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells.Cell Death Dis.20211212112510.1038/s41419‑021‑04413‑034862368
     [Google Scholar]
  18. RobeyR.W. MasseyP.R. Amiri-KordestaniL. BatesS.E. ABC transporters: Unvalidated therapeutic targets in cancer and the CNS.Anticancer. Agents Med. Chem.201010862563310.2174/18715201079447395721189132
     [Google Scholar]
  19. CalcagnoA.M. AmbudkarS.V. Analysis of expression of drug resistance-linked ABC transporters in cancer cells by quantitative RT-PCR.Methods Mol. Biol.201063712113210.1007/978‑1‑60761‑700‑6_620419432
     [Google Scholar]
  20. AfsarN.A. HaenischS. MateenA. UsmanA. UferM. AhmedK.Z. AhmadH.R. CascorbiI. Genotype frequencies of selected drug metabolizing enzymes and ABC drug transporters among breast cancer patients on FAC chemotherapy.Basic Clin. Pharmacol. Toxicol.2010107157057610.1111/j.1742‑7843.2009.00531.x20102361
     [Google Scholar]
  21. GaoN. LiY. LiJ. GaoZ. YangZ. LiY. LiuH. FanT. Long Non-Coding RNAs: The regulatory mechanisms, research strategies, and future directions in cancers.Front. Oncol.20201059881710.3389/fonc.2020.59881733392092
     [Google Scholar]
  22. ZhangX.Z. LiuH. ChenS.R. Mechanisms of long non- coding rnas in cancers and their dynamic regulations.Cancers (Basel)2020125124510.3390/cancers1205124532429086
     [Google Scholar]
  23. GilN. UlitskyI. Regulation of gene expression by cis-acting long non-coding RNAs.Nat. Rev. Genet.202021210211710.1038/s41576‑019‑0184‑531729473
     [Google Scholar]
  24. LiZ. ZhengJ. XiaQ. HeX. BaoJ. ChenZ. KatayamaH. YuD. ZhangX. XuJ. ZhuT. WangJ. Identification of specific long non-coding ribonucleic acid signatures and regulatory networks in prostate cancer in fine-needle aspiration biopsies.Front. Genet.2020116210.3389/fgene.2020.0006232117463
     [Google Scholar]
  25. QiX. ZhangD.H. WuN. XiaoJ.H. WangX. MaW. ceRNA in cancer: Possible functions and clinical implications.J. Med. Genet.2015521071071810.1136/jmedgenet‑2015‑10333426358722
     [Google Scholar]
  26. SongC. ZhangJ. QiH. FengC. ChenY. CaoY. BaL. AiB. WangQ. HuangW. LiC. SunH. Author Correction: The global view of mRNA-related ceRNA cross-talks across cardiovascular diseases.Sci. Rep.2018811101910.1038/s41598‑018‑29002‑830018284
     [Google Scholar]
  27. SongC. ZhangJ. QiH. FengC. ChenY. CaoY. BaL. AiB. WangQ. HuangW. LiC. SunH. The global view of mRNA-related ceRNA cross-talks across cardiovascular diseases.Sci. Rep.2017711018510.1038/s41598‑017‑10547‑z28860540
     [Google Scholar]
  28. YangC. WuD. GaoL. LiuX. JinY. WangD. WangT. LiX. Competing endogenous RNA networks in human cancer: Hypothesis, validation, and perspectives.Oncotarget2016712134791349010.18632/oncotarget.726626872371
     [Google Scholar]
  29. ZhouR.S. ZhangE.X. SunQ.F. YeZ.J. LiuJ.W. ZhouD.H. TangY. Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue.BMC Cancer201919177910.1186/s12885‑019‑5983‑831391008
     [Google Scholar]
  30. PuY. ZhaoF. LiY. CuiM. WangH. MengX. CaiS. The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.BMC Cancer20171714510.1186/s12885‑016‑3002‑x28073349
     [Google Scholar]
  31. ChenR. HongQ. JiangJ. ChenX. JiangZ. WangJ. LiuS. DuanS. ShiS. AGTR1 promoter hypermethylation in lung squamous cell carcinoma but not in lung adenocarcinoma.Oncol. Lett.20171444989499410.3892/ol.2017.682429085512
     [Google Scholar]
  32. WernerT.V. HartM. NickelsR. KimY.J. MengerM.D. BohleR.M. KellerA. LudwigN. MeeseE. MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2.Aging20179393295410.18632/aging.10120128340489
     [Google Scholar]
  33. JuracekJ StanikM VeselaP RadovaL DolezelJ SvobodaM SlabyO. Tumor expression of miR-34a-3p is an independent predictor of recurrence in non–muscle-invasive bladder cancer and promising additional factor to improve predictive value of EORTC nomogram.Urolog. Oncol.: Semin. Orig. Investig.2019373184.e1184.e710.1016/j.urolonc.2018.10.014
     [Google Scholar]
  34. GnanamonyM. DemirkhanyanL. GeL. SojitraP. BapanaS. NortonJ. GondiC. Circular dumbbell miR-34a-3p and -5p suppresses pancreatic tumor cell-induced angiogenesis and activates macrophages.Oncol. Lett.20202117510.3892/ol.2020.1233633365086
     [Google Scholar]
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LAMTOR5-AS1 Regulates Chemotherapy-induced Oxidative Stress via the miR-34a-3p/SIRT1/HNF4A Axis in Osteosarcoma Cells
Curr. Med. Chem. 32, 6633 (2025); https://doi.org/10.2174/0109298673316534240708111058
/content/journals/cmc/10.2174/0109298673316534240708111058
/content/journals/cmc/10.2174/0109298673316534240708111058
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  • Article Type:     Research Article
Keyword(s): cell proliferation; drug-resistance; LAMTOR5-AS1; long noncoding RNAs; miR-34a-3p; Osteosarcoma

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