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2000
Volume 25, Issue 11
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Introduction/Objective

Lung cancer causes hundreds of thousands of deaths each year worldwide. FHOD3 was reported to accelerate the progression of brain cancer. However, its role in lung cancer is not clear. This study aimed to investigate the role of FHOD3 in lung cancer.

Methods

The clinical significance of FHOD3 in lung cancer was analyzed based on the data from the TCGA database. The expression level of FHOD3 was detected by qPCR technology. Cell proliferation was detected by CCK-8 assay, and cell invasion was detected by transwell assay. The activity of caspase-3 was determined by the ELISA method, cell apoptosis was identified by TUNEL assay, and protein expression was measured by western blotting technology.

Results

Based on the TCGA data, FHOD3 was overexpressed in tumor tissues compared to the normal tissues. Patients with higher FHOD3 expression exhibited a worse survival rate. The expression levels of FHOD3 in lung cancer cell lines were much higher than that in normal cells. When FHOD3 was knocked down, the ability of cell proliferation and invasion was significantly inhibited. Cell apoptosis rate was increased reversely. The activity of caspase-3 was increased significantly. In addition, the expression level of cleaved caspase-3 was increased. The expression levels of Bax, caspase-8, and ICAD were also increased significantly. However, the expression of antiapoptotic molecule Bcl-2 was decreased reversely. This suggests that the caspase-3-mediated apoptosis signaling pathway was activated by FHOD3 knockdown.

Conclusion

FHOD3 was overexpressed and negatively associated with survival rate in lung cancer patients. FHOD3 regulates cell proliferation, invasion, and apoptosis through the caspase-3-mediated signaling pathway. This study indicates that FHOD3 is an important gene contributing to the progression of lung cancer and might be a new drug target for the therapy of lung cancer.

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References

  1. BadeB.C. Dela CruzC.S. Lung Cancer 2020.Clin. Chest Med.202041112410.1016/j.ccm.2019.10.001 32008623
    [Google Scholar]
  2. Abu RousF. SinghiE.K. SridharA. FaisalM.S. DesaiA. Lung Cancer Treatment Advances in 2022.Cancer Invest.2023411122410.1080/07357907.2022.2119479 36036470
    [Google Scholar]
  3. VránaD. Advances in the therapy of small cell lung cancer.Klin. Onkol.202134Suppl. 1667010.48095/ccko2021S66 34154332
    [Google Scholar]
  4. SiegelR.L. GiaquintoA.N. JemalA. Cancer statistics, 2024.CA Cancer J. Clin.2024741124910.3322/caac.21820 38230766
    [Google Scholar]
  5. KhanF. PandeyP. MishraR. ArifM. KumarA. JafriA. MazumderR. Elucidation of S-Allylcysteine Role in Inducing Apoptosis by Inhibiting PD-L1 Expression in Human Lung Cancer Cells.Anticancer. Agents Med. Chem.202121453254110.2174/1871520620666200728121929 32723260
    [Google Scholar]
  6. Pratibha Pandey Fahad Khan Prashant Chauhan, Fevzi Bardakci; Nujud Almuzaini; Mohd Saeed; Almuzaini, N.; Abdalla, R.A.H.; Singh, S.K.; Saeed, M. Elucidation of the inhibitory potential of flavonoids against PKP1 protein in non-small cell lung cancer.Cell. Mol. Biol.20226811909610.14715/cmb/2022.68.11.15 37114302
    [Google Scholar]
  7. ChauhanP. PandeyP. RamniwasS. KhanF. Review Deciphering the Potential of Nanotherapeutics in Lung Cancer Management.Curr. Cancer Drug Targets20242210.2174/0115680096302203240308104740 38561624
    [Google Scholar]
  8. MelicharB. Biomarkers in the management of lung cancer: changing the practice of thoracic oncology.Clin. Chem. Lab. Med.202361590692010.1515/cclm‑2022‑1108 36384005
    [Google Scholar]
  9. LimZ.F. MaP.C. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy.J. Hematol. Oncol.201912113410.1186/s13045‑019‑0818‑2 31815659
    [Google Scholar]
  10. WadowskaK. Bil-LulaI. TrembeckiŁ. Śliwińska-MossońM. Genetic Markers in Lung Cancer Diagnosis: A Review.Int. J. Mol. Sci.20202113456910.3390/ijms21134569 32604993
    [Google Scholar]
  11. ChiuY.T. HusainA. SzeK.M.F. HoD.W.H. SuarezE.M.S. WangX. LeeE. MaH.T. LeeJ.M.F. ChanL.K. NgI.O.L. Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC.Hepatology20237851368138310.1097/HEP.0000000000000266 36632999
    [Google Scholar]
  12. SunY. ShenW. HuS. LyuQ. WangQ. WeiT. ZhuW. ZhangJ. METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy.J. Exp. Clin. Cancer Res.20234216510.1186/s13046‑023‑02638‑9 36932427
    [Google Scholar]
  13. OchoaJ.P. LopesL.R. Perez-BarbeitoM. Cazón-VarelaL. de la Torre-CarpenteM.M. Sonicheva-PatersonN. De Uña-IglesiasD. QuinnE. Kuzmina-KrutetskayaS. GarroteJ.A. ElliottP.M. MonserratL. Deletions of specific exons ofFHOD3 detected by next‐generation sequencing are associated with hypertrophic cardiomyopathy.Clin. Genet.2020981869010.1111/cge.13759 32335906
    [Google Scholar]
  14. VodnjovN. ToplišekJ. MaverA. ČuturiloG. JakličH. TeranN. VišnjarT. Škrjanec PušenjakM. HodžićA. MiljanovićO. PeterlinB. WritzlK. A novel splice-site FHOD3 founder variant is a common cause of hypertrophic cardiomyopathy in the population of the Balkans–A cohort study.PLoS One20231812e029496910.1371/journal.pone.0294969 38051749
    [Google Scholar]
  15. HuangS. PuT. WeiW. XuR. WuY. Exome sequencing identifies a FHOD3 p.S527del mutation in a Chinese family with hypertrophic cardiomyopathy.J. Gene Med.2020223e314610.1002/jgm.3146 31742804
    [Google Scholar]
  16. YuJ. ShiW. ZhaoR. ShenW. LiH. FHOD3 promotes carcinogenesis by regulating RhoA/ROCK1/LIMK1 signaling pathway in medulloblastoma.Clin. Transl. Oncol.202022122312232310.1007/s12094‑020‑02389‑5 32447646
    [Google Scholar]
  17. PaulN.R. AllenJ.L. ChapmanA. Morlan-MairalM. ZindyE. JacquemetG. Fernandez del AmaL. FerizovicN. GreenD.M. HoweJ.D. EhlerE. HurlstoneA. CaswellP.T. α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3.J. Cell Biol.201521061013103110.1083/jcb.201502040 26370503
    [Google Scholar]
  18. ChaiL. LiJ. LvZ. An integrated analysis of cancer genes in thyroid cancer.Oncol. Rep.201635296297010.3892/or.2015.4466 26718127
    [Google Scholar]
  19. ZhangY. LiN. YangL. JiaW. LiZ. ShaoQ. ZhanX. Quantitative phosphoproteomics reveals molecular pathway network alterations in human early-stage primary hepatic carcinomas: potential for 3P medical approach.EPMA J.202314347750210.1007/s13167‑023‑00335‑3 37605650
    [Google Scholar]
  20. MonzoP. ChongY.K. Guetta-TerrierC. KrishnasamyA. SatheS.R. YimE.K.F. NgW.H. AngB.T. TangC. LadouxB. GauthierN.C. SheetzM.P. Mechanical confinement triggers glioma linear migration dependent on formin FHOD3.Mol. Biol. Cell20162781246126110.1091/mbc.E15‑08‑0565 26912794
    [Google Scholar]
  21. TomczakK. CzerwińskaP. WiznerowiczM. Review The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge.Contemp. Oncol. (Pozn.)20151A1A687710.5114/wo.2014.47136 25691825
    [Google Scholar]
  22. PandeyP. KhanF. FarhanM. JafriA. Elucidation of rutin’s role in inducing caspase-dependent apoptosis via HPV-E6 and E7 down-regulation in cervical cancer HeLa cells.Biosci. Rep.2021416BSR2021067010.1042/BSR20210670 34109976
    [Google Scholar]
  23. de SousaV.M.L. CarvalhoL. Heterogeneity in Lung Cancer.Pathobiology2018851-29610710.1159/000487440 29635240
    [Google Scholar]
  24. ManiosK. TsiambasE. StavrakisI. StamatelopoulosA. KavantzasN. AgrogiannisG. C LazarisA. c-Fos/c-Jun transcription factors in non-small cell lung carcinoma.JBUON202025521412143 33277827
    [Google Scholar]
  25. DhanasekaranR. DeutzmannA. Mahauad-FernandezW.D. HansenA.S. GouwA.M. FelsherD.W. The MYC oncogene — the grand orchestrator of cancer growth and immune evasion.Nat. Rev. Clin. Oncol.2022191233610.1038/s41571‑021‑00549‑2 34508258
    [Google Scholar]
  26. VuralS. MuhtaroğluA. UygurF.A. The relationship between preoperative CEA and CA19-9 status and patient characteristics and lymph node involvement in early-stage colon cancer.Eur. Rev. Med. Pharmacol. Sci.2023271045634569 37259737
    [Google Scholar]
  27. HanahanD. Hallmarks of Cancer: New Dimensions.Cancer Discov.2022121314610.1158/2159‑8290.CD‑21‑1059 35022204
    [Google Scholar]
  28. RibattiD. A revisited concept: Contact inhibition of growth. From cell biology to malignancy.Exp. Cell Res.20173591171910.1016/j.yexcr.2017.06.012 28642051
    [Google Scholar]
  29. NakamuraF. The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation.Int. J. Mol. Sci.2024254213510.3390/ijms25042135 38396812
    [Google Scholar]
  30. ShiY. LiY. WuB. ZhongC. LangQ. LiangZ. ZhangY. LvC. HanS. YuY. XuF. TianY. Normalization of tumor vasculature: A potential strategy to increase the efficiency of immune checkpoint blockades in cancers.Int. Immunopharmacol.202211010896810.1016/j.intimp.2022.108968 35764018
    [Google Scholar]
  31. de AlmeidaL.G.N. ThodeH. EslambolchiY. ChopraS. YoungD. GillS. DevelL. DufourA. Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology.Pharmacol. Rev.202274371477010.1124/pharmrev.121.000349 35738680
    [Google Scholar]
  32. NanoM. MontellD.J. Apoptotic signaling: Beyond cell death.Semin. Cell Dev. Biol.2024156223410.1016/j.semcdb.2023.11.002 37988794
    [Google Scholar]
  33. LamkanfiM. FestjensN. DeclercqW. BergheT.V. VandenabeeleP. Caspases in cell survival, proliferation and differentiation.Cell Death Differ.2007141445510.1038/sj.cdd.4402047 17053807
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): caspase cascades responses; Caspase-3; FHOD3; ICAD; lung cancer; TCGA
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