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image of Metformin Inhibits the Growth of Hypopharyngeal Squamous Cell Carcinoma of Fadu Cell and Down-Regulates LncAROD to Improve Prognosis
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Abstract

Background

Hypopharyngeal Squamous Cell Carcinoma (HSCC) is associated with a poor prognosis due to challenges in early detection, early metastasis, and limited treatment options.

Objective

This study aims to investigate the effect of metformin on HSCC and identify potential prognostic factors associated with this carcinoma.

Methods

The effects of in HSCC cells were tested by functional assays . A xenograft tumor model was established, which was further examined by H&E staining, immunohistochemistry, and transmission electron microscopy (TEM). RNA sequencing analysis was employed to investigate the effects of metformin on gene expression and associated pathways. Bioinformatic analysis was further conducted to elucidate potential mechanisms and their correlation with gene expression, the tumor immune microenvironment, and survival prognosis. Finally, we further assessed the effect on FaDu cells by knocking down lncAROD using siRNAs.

Results

The results demonstrated that metformin significantly reduced cell viability and migration, while promoting apoptosis and inducing cell cycle arrest in FaDu cells. WB analysis revealed that metformin inhibits the development of FaDu cells, possibly through the EMT pathway. studies indicate that metformin effectively inhibits tumor growth, promotes apoptosis, and autophagy. RNA-seq analysis revealed that metformin led to the upregulation of 1,697 genes and the downregulation of 858 genes, particularly highlighting a significant reduction in lncAROD, which were subsequently verified by qRT-PCR. Bioinformatic analysis demonstrated that lncAROD is highly expressed, with patients exhibiting higher levels of lncAROD showing poorer prognoses. Knockdown of lncAROD can reduce the proliferation, migration, and invasion of FaDu cells.

Conclusion

This finding presents a novel approach to the clinical management of HSCC, indicating that metformin influences various processes related to the growth and progression of HSCC. Specifically, it reduces lncAROD expression and inhibits tumor progression, suggesting that lncAROD may serve as a valuable biomarker for evaluating the prognosis of HSCC.

© 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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2025-10-29
2025-12-14

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References

  1. Jakstas T. Bartnykaite A. Padervinskis E. Vegiene A. Juozaityte E. Uloza V. Ugenskiene R. The association of TP53, BCL2, BAX and NOXA SNPs and laryngeal squamous cell carcinoma development. Int. J. Mol. Sci. 2024 25 21 11849 10.3390/ijms252111849 39519400
    [Google Scholar]
  2. Cai Z. Chen L. Chen S. Fang R. Chen X. Lei W. Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma. Cell Commun. Signal. 2023 21 1 292 10.1186/s12964‑023‑01312‑z 37853464
    [Google Scholar]
  3. Luo X. Huang X. Liu S. Wang X. Luo J. Xiao J. Wang K. Qu Y. Chen X. Zhang Y. Wang J. Zhang J. Xu G. Gao L. Wu R. Yi J. Response-Adapted treatment following radiotherapy in patients with resectable locally advanced hypopharyngeal carcinoma. JAMA Netw. Open 2022 5 2 e220165 10.1001/jamanetworkopen.2022.0165 35191967
    [Google Scholar]
  4. Visini M. Giger R. Shelan M. Elicin O. Anschuetz L. Predicting factors for oncological and functional outcome in hypopharyngeal cancer. Laryngoscope 2021 131 5 E1543 E1549 10.1002/lary.29186 33098325
    [Google Scholar]
  5. Tassler A.B. Gooding W.E. Ferris R.L. Hypopharyngeal cancer treatment: Does initial surgery confer survival benefit? Head Neck 2019 41 7 2167 2173 10.1002/hed.25687 30779398
    [Google Scholar]
  6. Kwon D.I. Miles B.A. Hypopharyngeal carcinoma: Do you know your guidelines? Head Neck 2019 41 3 569 576 10.1002/hed.24752 30570183
    [Google Scholar]
  7. Solomon B. Young R.J. Rischin D. Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments. Semin. Cancer Biol. 2018 52 Pt 2 228 240 10.1016/j.semcancer.2018.01.008 29355614
    [Google Scholar]
  8. Desai N. Divatia M.K. Jadhav A. Wagh A. Aggressive cutaneous squamous cell carcinoma of the head and neck: A review. Curr. Oncol. 2023 30 7 6634 6647 10.3390/curroncol30070487 37504347
    [Google Scholar]
  9. Panda S. Sakthivel P. Gurusamy K.S. Sharma A. Thakar A. Treatment options for resectable hypopharyngeal squamous cell carcinoma: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2022 17 11 e0277460 10.1371/journal.pone.0277460 36445884
    [Google Scholar]
  10. Ruffin A.T. Li H. Vujanovic L. Zandberg D.P. Ferris R.L. Bruno T.C. Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment. Nat. Rev. Cancer 2023 23 3 173 188 10.1038/s41568‑022‑00531‑9 36456755
    [Google Scholar]
  11. Xia Y. Sun M. Huang H. Jin W.L. Drug repurposing for cancer therapy. Signal Transduct. Target. Ther. 2024 9 1 92 10.1038/s41392‑024‑01808‑1 38637540
    [Google Scholar]
  12. Singhal S. Maheshwari P. Krishnamurthy P.T. Patil V.M. Drug repurposing strategies for non-cancer to cancer therapeutics. Anticancer. Agents Med. Chem. 2022 22 15 2726 2756 10.2174/1871520622666220317140557 35301945
    [Google Scholar]
  13. Jin M.Z. Jin W.L. The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct. Target. Ther. 2020 5 1 166 10.1038/s41392‑020‑00280‑x 32843638
    [Google Scholar]
  14. Fu Z. Zhang X. Gao Y. Fan J. Gao Q. Enhancing the anticancer immune response with the assistance of drug repurposing and delivery systems. Clin. Transl. Med. 2023 13 7 e1320 10.1002/ctm2.1320 37403792
    [Google Scholar]
  15. Jin M. Zeng B. Liu Y. Jin L. Hou Y. Liu C. Liu W. Wu H. Chen L. Gao Z. Huang W. Co-delivery of repurposing itraconazole and vegf sirna by composite nanoparticulate system for collaborative anti-angiogenesis and anti-tumor efficacy against breast cancer. Pharmaceutics 2022 14 7 1369 10.3390/pharmaceutics14071369 35890264
    [Google Scholar]
  16. Fayyaz S. Atia-Tul-Wahab; Irshad, R.; Siddiqui, R.A.; Choudhary, M.I. Antidepressant sertraline hydrochloride inhibits the growth of HER2+ AU565 breast cancer cell line through induction of apoptosis and cell cycle arrest. Anticancer. Agents Med. Chem. 2024 24 14 1038 1046 10.2174/0118715206304918240509111700 38766835
    [Google Scholar]
  17. Anwer M.S. Abdel-Rasol M.A. El-Sayed W.M. Emerging therapeutic strategies in glioblastsoma: Drug repurposing, mechanisms of resistance, precision medicine, and technological innovations. Clin. Exp. Med. 2025 25 1 117 10.1007/s10238‑025‑01631‑0 40223032
    [Google Scholar]
  18. Wang Y. Yang Y. Chen S. Wang J. DeepDRK: A deep learning framework for drug repurposing through kernel-based multi-omics integration. Brief. Bioinform. 2021 22 5 bbab048 10.1093/bib/bbab048 33822890
    [Google Scholar]
  19. Abdel-Wahab A.F. Mahmoud W. Al-Harizy R.M. Targeting glucose metabolism to suppress cancer progression: Prospective of anti-glycolytic cancer therapy. Pharmacol. Res. 2019 150 104511 10.1016/j.phrs.2019.104511 31678210
    [Google Scholar]
  20. Foretz M. Guigas B. Viollet B. Metformin: Update on mechanisms of action and repurposing potential. Nat. Rev. Endocrinol. 2023 19 8 460 476 10.1038/s41574‑023‑00833‑4 37130947
    [Google Scholar]
  21. Coyle C. Cafferty F.H. Vale C. Langley R.E. Metformin as an adjuvant treatment for cancer: A systematic review and meta-analysis. Ann. Oncol. 2016 27 12 2184 2195 10.1093/annonc/mdw410 27681864
    [Google Scholar]
  22. Sun Y. Cheng J. Nie D. Fang Q. Li C. Zhang Y. Metformin inhibits cell proliferation and ACTH secretion in AtT20 cells via regulating the MAPK pathway. Mol. Cell. Endocrinol. 2024 582 112140 10.1016/j.mce.2023.112140 38147953
    [Google Scholar]
  23. Rêgo D.F. Elias S.T. Amato A.A. Canto G.D.L. Guerra E.N.S. Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review. Oncol. Lett. 2017 13 2 554 566 10.3892/ol.2016.5526 28356929
    [Google Scholar]
  24. Vasan K. Werner M. Chandel N.S. Mitochondrial metabolism as a target for cancer therapy. Cell Metab. 2020 32 3 341 352 10.1016/j.cmet.2020.06.019 32668195
    [Google Scholar]
  25. Chen Y.H. Yang S.F. Yang C.K. Tsai H.D. Chen T.H. Chou M.C. Hsiao Y.H. Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells. Mol. Med. Rep. 2020 23 1 88 10.3892/mmr.2020.11725 33236135
    [Google Scholar]
  26. Yang J. Zhou Y. Xie S. Wang J. Li Z. Chen L. Mao M. Chen C. Huang A. Chen Y. Zhang X. Khan N.U.H. Wang L. Zhou J. Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer. J. Exp. Clin. Cancer Res. 2021 40 1 206 10.1186/s13046‑021‑02012‑7 34162423
    [Google Scholar]
  27. Padilla J. Lee J. A novel therapeutic target, BACH1, regulates cancer metabolism. Cells 2021 10 3 634 10.3390/cells10030634 33809182
    [Google Scholar]
  28. Huang X. Sun T. Wang J. Hong X. Chen H. Yan T. Zhou C. Sun D. Yang C. Yu T. Su W. Du W. Xiong H. Metformin reprograms tryptophan metabolism to stimulate CD8+ T-cell function in colorectal cancer. Cancer Res. 2023 83 14 2358 2371 10.1158/0008‑5472.CAN‑22‑3042 37195082
    [Google Scholar]
  29. Morale M.G. Tamura R.E. Rubio I.G.S. Metformin and cancer hallmarks: Molecular mechanisms in thyroid, prostate and head and neck cancer models. Biomolecules 2022 12 3 357 10.3390/biom12030357 35327549
    [Google Scholar]
  30. Triggle C.R. Mohammed I. Bshesh K. Marei I. Ye K. Ding H. MacDonald R. Hollenberg M.D. Hill M.A. Metformin: Is it a drug for all reasons and diseases? Metabolism 2022 133 155223 10.1016/j.metabol.2022.155223 35640743
    [Google Scholar]
  31. Tufail M. Jiang C.H. Li N. Altered metabolism in cancer: Insights into energy pathways and therapeutic targets. Mol. Cancer 2024 23 1 203 10.1186/s12943‑024‑02119‑3 39294640
    [Google Scholar]
  32. Halma M. Tuszynski J. Marik P. Cancer metabolism as a therapeutic target and review of interventions. Nutrients 2023 15 19 4245 10.3390/nu15194245 37836529
    [Google Scholar]
  33. Kroemer G. Pouyssegur J. Tumor cell metabolism: Cancer’s Achilles’ heel. Cancer Cell 2008 13 6 472 482 10.1016/j.ccr.2008.05.005 18538731
    [Google Scholar]
  34. Tan Y.T. Lin J.F. Li T. Li J.J. Xu R.H. Ju H.Q. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun. 2021 41 2 109 120 10.1002/cac2.12108 33119215
    [Google Scholar]
  35. Zhou H. Hao X. Zhang P. He S. Noncoding RNA mutations in cancer. Wiley Interdiscip. Rev. RNA 2023 14 6 e1812 10.1002/wrna.1812 37544928
    [Google Scholar]
  36. Ahmad M. Weiswald L.B. Poulain L. Denoyelle C. Meryet-Figuiere M. Involvement of lncRNAs in cancer cells migration, invasion and metastasis: Cytoskeleton and ECM crosstalk. J. Exp. Clin. Cancer Res. 2023 42 1 173 10.1186/s13046‑023‑02741‑x 37464436
    [Google Scholar]
  37. Li D. Feng J. Wu T. Wang Y. Sun Y. Ren J. Liu M. Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am. J. Pathol. 2013 182 1 64 70 10.1016/j.ajpath.2012.08.042 23141928
    [Google Scholar]
  38. Xu E. Liang X. Ji Z. Zhao S. Li L. Lang J. Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma. Eur. Arch. Otorhinolaryngol. 2020 277 2 611 621 10.1007/s00405‑019‑05732‑x 31792655
    [Google Scholar]
  39. Garcia-Padilla C. Lozano-Velasco E. Muñoz-Gallardo M.M. Castillo-Casas J.M. Caño-Carrillo S. Martínez-Amaro F.J. García-López V. Aránega A. Franco D. García-Martínez V. López-Sánchez C. LncRNA H19 impairs chemo and radiotherapy in tumorigenesis. Int. J. Mol. Sci. 2022 23 15 8309 10.3390/ijms23158309 35955440
    [Google Scholar]
  40. Lin D. Shen L. Luo M. Zhang K. Li J. Yang Q. Zhu F. Zhou D. Zheng S. Chen Y. Zhou J. Circulating tumor cells: Biology and clinical significance. Signal Transduct. Target. Ther. 2021 6 1 404 10.1038/s41392‑021‑00817‑8 34803167
    [Google Scholar]
  41. Zhang H. Lu X. Lu B. Gullo G. Chen L. Measuring the composition of the tumor microenvironment with transcriptome analysis: past, present and future. Future Oncol. 2024 20 17 1207 1220 10.2217/fon‑2023‑0658 38362731
    [Google Scholar]
  42. Mollaei M. Hassan Z.M. Khorshidi F. Langroudi L. Chemotherapeutic drugs: Cell death- and resistance-related signaling pathways. Are they really as smart as the tumor cells? Transl. Oncol. 2021 14 5 101056 10.1016/j.tranon.2021.101056 33684837
    [Google Scholar]
  43. Zheng D. Shen Y. Wei Z. Wan X. Xie M. Yao H. Wang Z. Transcriptome sequencing reveals a lncRNA–mRNA interaction network in extramammary Paget’s disease. BMC Med. Genomics 2021 14 1 291 10.1186/s12920‑021‑01135‑2 34895219
    [Google Scholar]
  44. Tian W. Zhou J. Chen M. Qiu L. Li Y. Zhang W. Guo R. Lei N. Chang L. Bioinformatics analysis of the role of aldolase A in tumor prognosis and immunity. Sci. Rep. 2022 12 1 11632 10.1038/s41598‑022‑15866‑4 35804089
    [Google Scholar]
  45. Nuth M. Benakanakere M. Ricciardi R. Discovery of a potent cytotoxic agent that promotes G 2/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line. Int. J. Oncol. 2022 60 4 41 10.3892/ijo.2022.5331 35211767
    [Google Scholar]
  46. Rêgo D.F. Pavan L.M.C. Elias S.T. De Luca Canto G. Guerra E.N.S. Effects of metformin on head and neck cancer: A systematic review. Oral Oncol. 2015 51 5 416 422 10.1016/j.oraloncology.2015.01.007 25636350
    [Google Scholar]
  47. Wu X. Yeerna H. Goto Y. Ando T. Wu V.H. Zhang X. Wang Z. Amornphimoltham P. Murphy A.N. Tamayo P. Chen Q. Lippman S.M. Gutkind J.S. Metformin inhibits progression of head and neck squamous cell carcinoma by acting directly on carcinoma-initiating cells. Cancer Res. 2019 79 17 4360 4370 10.1158/0008‑5472.CAN‑18‑3525 31292160
    [Google Scholar]
  48. Di Matteo S. Nevi L. Overi D. Landolina N. Faccioli J. Giulitti F. Napoletano C. Oddi A. Marziani A.M. Costantini D. Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells. Sci. Rep. 2021 11 1 2557 10.1038/s41598‑021‑81172‑0
    [Google Scholar]
  49. Nguyen M.T. Choe H.C. Kim B.H. Ahn S.G. A new link between apoptosis induced by the metformin derivative HL156A and autophagy in oral squamous cell carcinoma. Eur. J. Pharmacol. 2022 920 174859 10.1016/j.ejphar.2022.174859 35219727
    [Google Scholar]
  50. Xavier A.E.T. Veronez L.C. Nagano L.F.P. Correa C.A.P. Baroni M. Ramos M.S. Queiroz R.G.P. Fernandes Molina C.A. Yunes J.A. Brandalise S.R. Antonini S.A.R. Tone L.G. Valera E.T. Scrideli C.A. Low PRKAB2 expression Is Associated with Poor Outcomes in Pediatric Adrenocortical Tumors, and Treatment with Rottlerin Increases the PRKAB2 Level and Inhibits Tumorigenic Aspects in the NCI-H295R Adrenocortical Cancer Cell Line. Cancers 2024 16 6 1094 10.3390/cancers16061094 38539429
    [Google Scholar]
  51. Wu J. Zhang D. Li J. Deng X. Liang G. Long Y. He X. Dai T. Ren D. MACC1 induces autophagy to regulate proliferation, apoptosis, migration and invasion of squamous cell carcinoma. Oncol. Rep. 2017 38 4 2369 2377 10.3892/or.2017.5889 28791376
    [Google Scholar]
  52. Xue Q. Kang R. Klionsky D.J. Tang D. Liu J. Chen X. Copper metabolism in cell death and autophagy. Autophagy 2023 19 8 2175 2195 10.1080/15548627.2023.2200554 37055935
    [Google Scholar]
  53. Safavi K. Abedpoor N. Hajibabaie F. Ka E. Mitigating diabetic cardiomyopathy: The synergistic potential of sea buckthorn and metformin explored via bioinformatics and chemoinformatics. Biology 2025 14 4 361 10.3390/biology14040361 40282226
    [Google Scholar]
  54. Liao Q. Xu W. Luo Q. Wen X. Zhenqing recipe relieves diabetic nephropathy through the SIK1/SREBP-1c axis in type 2 diabetic rats. Am. J. Transl. Res. 2021 13 12 13776 13783 35035716
    [Google Scholar]
  55. Shi X. Zhang X. Huang X. Zhang R. Pan S. Huang S. Wang Y. Ke Y. Guo W. Liu X. Hao Y. Li Y. Zhao X. Sun Y. Li J. Ma H. Zhao X.N. 6 -methyladenosine-mediated upregulation of LNCAROD confers radioresistance in esophageal squamous cell carcinoma through stabilizing PARP1. Clin. Transl. Med. 2024 14 10 e70039 10.1002/ctm2.70039 39367700
    [Google Scholar]
  56. Ban Y. Tan P. Cai J. Li J. Hu M. Zhou Y. Mei Y. Tan Y. Li X. Zeng Z. Xiong W. Li G. Li X. Yi M. Xiang B. LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma. Mol. Oncol. 2020 14 6 1282 1296 10.1002/1878‑0261.12676 32216017
    [Google Scholar]
  57. Tang J. Zhang J. Lu Y. He J. Wang H. Liu B. Tu C. Li Z. Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications. Biomark. Res. 2023 11 1 42 10.1186/s40364‑023‑00484‑7 37069649
    [Google Scholar]
  58. Cerk S. Schwarzenbacher D. Adiprasito J. Stotz M. Hutterer G. Gerger A. Ling H. Calin G. Pichler M. Current status of long non-coding RNAs in 0. Int. J. Mol. Sci. 2016 17 9 1485 10.3390/ijms17091485 27608009
    [Google Scholar]
  59. Qian Y. Shi L. Luo Z. Long Non-coding RNAs in cancer: Implications for diagnosis, prognosis, and therapy. Front. Med. 2020 7 612393 10.3389/fmed.2020.612393 33330574
    [Google Scholar]
  60. Ansari S. Nikpour P. LNCAROD promotes the proliferation and migration of gastric cancer: a bioinformatics analysis and experimental validation. Funct. Integr. Genomics 2023 23 1 34 10.1007/s10142‑022‑00954‑5 36625949
    [Google Scholar]
  61. Toden S. Zumwalt T.J. Goel A. Non-coding RNAs and potential therapeutic targeting in cancer. Biochim. Biophys. Acta Rev. Cancer 2021 1875 1 188491 10.1016/j.bbcan.2020.188491 33316377
    [Google Scholar]
  62. Dong Y. Hu H. Zhang X. Zhang Y. Sun X. Wang H. Kan W. Tan M. Shi H. Zang Y. Li J. Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis. Signal Transduct. Target. Ther. 2023 8 1 95 10.1038/s41392‑022‑01302‑6 36872368
    [Google Scholar]
  63. Allgayer H. Mahapatra S. Mishra B. Swain B. Saha S. Khanra S. Kumari K. Panda V.K. Malhotra D. Patil N.S. Leupold J.H. Kundu G.C. Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: The status quo of methods and experimental models 2025. Mol. Cancer 2025 24 1 167 10.1186/s12943‑025‑02338‑2 40483504
    [Google Scholar]
  64. Dong B. Qiu Z. Wu Y. Tackle epithelial-mesenchymal transition with epigenetic drugs in cancer. Front. Pharmacol. 2020 11 596239 10.3389/fphar.2020.596239 33343366
    [Google Scholar]
  65. Dumitru C.S. Ceausu A.R. Comsa S. Raica M. Loss of E-Cadherin expression correlates with ki-67 in head and neck squamous cell carcinoma. In Vivo 2022 36 3 1150 1154 10.21873/invivo.12814 35478157
    [Google Scholar]
  66. Yang H.L. Chang C.W. Vadivalagan C. Pandey S. Chen S.J. Lee C.C. Hseu J.H. Hseu Y.C. Coenzyme Q0 inhibited the NLRP3 inflammasome, metastasis/EMT, and Warburg effect by suppressing hypoxia-induced HIF-1α expression in HNSCC cells. Int. J. Biol. Sci. 2024 20 8 2790 2813 10.7150/ijbs.93943 38904007
    [Google Scholar]
  67. Na T.Y. Schecterson L. Mendonsa A.M. Gumbiner B.M. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. Proc. Natl. Acad. Sci. USA 2020 117 11 5931 5937 10.1073/pnas.1918167117 32127478
    [Google Scholar]
  68. Loh C.Y. Chai J. Tang T. Wong W. Sethi G. Shanmugam M. Chong P. Looi C. The e-cadherin and n-cadherin switch in epithelial-to-mesenchymal transition: Signaling, therapeutic implications, and challenges. Cells 2019 8 10 1118 10.3390/cells8101118 31547193
    [Google Scholar]
  69. Gao S. Hu J. Wu X. Liang Z. PMA treated THP-1-derived-IL-6 promotes EMT of SW48 through STAT3/ERK-dependent activation of Wnt/β-catenin signaling pathway. Biomed. Pharmacother. 2018 108 618 624 10.1016/j.biopha.2018.09.067 30243096
    [Google Scholar]
  70. Ntini E. Louloupi A. Liz J. Muino J.M. Marsico A. Ørom U.A.V. Long ncRNA A-ROD activates its target gene DKK1 at its release from chromatin. Nat. Commun. 2018 9 1 1636 10.1038/s41467‑018‑04100‑3 29691407
    [Google Scholar]
  71. Liang L. Tu Y. Lu J. Wang P. Guo Z. Wang Q. Guo K. Lan R. Li H. Liu P. Dkk1 exacerbates doxorubicin-induced cardiotoxicity by inhibiting the Wnt/β-catenin signaling pathway. J. Cell Sci. 2019 132 10 jcs228478 10.1242/jcs.228478 31028181
    [Google Scholar]
  72. Jiang H. Zhang Z. Yu Y. Chu H.Y. Yu S. Yao S. Zhang G. Zhang B.T. Drug discovery of DKK1 inhibitors. Front. Pharmacol. 2022 13 847387 10.3389/fphar.2022.847387 35355709
    [Google Scholar]
  73. Xue W. Yang L. Chen C. Ashrafizadeh M. Tian Y. Sun R. Wnt/β-catenin-driven EMT regulation in human cancers. Cell. Mol. Life Sci. 2024 81 1 79 10.1007/s00018‑023‑05099‑7 38334836
    [Google Scholar]
  74. Bai Y. Sha J. Kanno T. The role of carcinogenesis-related biomarkers in the wnt pathway and their effects on epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma. Cancers 2020 12 3 555 10.3390/cancers12030555 32121061
    [Google Scholar]
  75. Zhou G. Wu H. Lin J. Lin R. Feng B. Liu Z. TRIM21 is decreased in colitis-associated cancer and negatively regulates epithelial carcinogenesis. Inflamm. Bowel Dis. 2021 27 4 458 468 10.1093/ibd/izaa229 32860065
    [Google Scholar]
  76. Zhang T. Pabla S. Lenzo F.L. Conroy J.M. Nesline M.K. Glenn S.T. Papanicolau-Sengos A. Burgher B. Giamo V. Andreas J. Wang Y. Bshara W. Madden K.G. Shirai K. Dragnev K. Tafe L.J. Gupta R. Zhu J. Labriola M. McCall S. George D.J. Ghatalia P. Dayyani F. Edwards R. Park M.S. Singh R. Jacob R. George S. Xu B. Zibelman M. Kurzrock R. Morrison C. Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients. OncoImmunology 2020 9 1 1773200 10.1080/2162402X.2020.1773200 32923131
    [Google Scholar]
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Metformin Inhibits the Growth of Hypopharyngeal Squamous Cell Carcinoma of Fadu Cell and Down-Regulates LncAROD to Improve Prognosis
Bentham Science Publishers ; https://doi.org/10.2174/0118715206427268251006112304
/content/journals/acamc/10.2174/0118715206427268251006112304
/content/journals/acamc/10.2174/0118715206427268251006112304
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  • Article Type:     Research Article
Keywords: fadu cell line ; lncAROD ; prognosis ; hypopharyngeal squamous cell carcinoma (HSCC) ; cancer biomarkers ; Metformin

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