Skip to content
2000
image of Mir-338-3p Increases the Sensitivity to Oxaliplatin via Reversing Epithelial-mesenchymal Transition in Hepatocellular Carcinoma Cells

Abstract

Objective

Oxaliplatin (OXA) is commonly used in combination therapy for patients with advanced hepatocellular carcinoma. While the emergence of acquired resistance dramatically reduces its efficacy. It was previously found that the sensitivity of drug-resistant hepatocellular carcinoma cells to OXA could be enhanced by a synthesized ethyl derivative (patented) of epigallocatechin-3-gallate, and also initially found that the reversal mechanism might be related to the miR-338-3p/HIF-1α/ TWIST pathway. In this study, the function of the miR-338-3p/HIF-1α / TWIST pathway was investigated in OXA-resistant hepatocellular carcinoma cells, particularly its involvement in reversing chemoresistance mediated by EMT.

Methods

The cell viability, migration, invasion, and epithelial-mesenchymal transition markers of SMMC-7721 and SMMC-7721/OXA cells were measured using the MTT assay, wound healing assay, transwell assay, western blot, and qRT-PCR. The effects of miR-338-3p overexpression were evaluated by transfecting cells with miR-338-3p mimic or negative control mimic.

Results and Discussion

The SMMC-7721/OXA cells exhibited an epithelial-mesenchymal transition phenotype, characterized by increased migration and invasion, reduced E-cadherin, and elevated vimentin expression. The miR-338-3p expression was dramatically down-regulated in SMMC-7721/OXA cells. Overexpression of miR-338-3p enhanced OXA sensitivity, with the IC value of OXA decreasing from 51.23 μM to 19.26 μM, reversed the epithelial-mesenchymal transition phenotype, and reduced the expression of hypoxia-inducible factor-1α and twist family bHLH transcription factor 1, key regulators of epithelial-mesenchymal transition. The results indicated that the miR-338-3p regulates epithelial-mesenchymal transition and chemoresistance in OXA-resistant hepatocellular carcinoma cells by targeting hypoxiainducible factor-1α and subsequently down-regulating twist family bHLH transcription factor 1.

Conclusion

This study implies that the resistance of SMMC-7721/OXA cells to OXA is likely related to the acquisition of the EMT phenotype. The up-regulating miR-338-3p could be a new treatment method for over-coming OXA resistance in hepatocellular carcinoma.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/pra/10.2174/0115748928408751251113182005
2026-01-12
2026-02-26

  • From This Site

    /content/journals/pra/10.2174/0115748928408751251113182005
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Huang C. Wang S.H. Liu T.T. Epigallocatechin Gallate derivative y6 reverses oxaliplatin resistance in hepatocellular carcinoma via targeting the MiR-338-3p/HIF-1α/TWIST axis to Inhibit EMT. Recent Patents Anticancer Drug Discov. 2024 19 19 10.2174/0115748928293750240619092747
    [Google Scholar]
  2. Liang G Li L Chen R-L Sun Y-W Tang A-Z Liu B-M The application of Egcg structurally modified derivatives in the preparation of vascular regulatory drugs. CN patent 105030756A 2015
    [Google Scholar]
  3. Xu W. Liao S. Hu Y. Huang Y. Zhou J. Upregulation of miR-3130-5p Enhances Hepatocellular Carcinoma Growth by Suppressing Ferredoxin 1: miR-3130-5p Enhances HCC Growth via Inhibiting FDX1. Curr. Mol. Pharmacol. 2025 17 17 10.2174/0118761429358008250305070518 40103455
    [Google Scholar]
  4. Zhou Y. Gu J. Yu H. Screening and identification of ESR1 as a Target of icaritin in hepatocellular carcinoma: Evidence from bibliometrics and bioinformatic analysis. Curr. Mol. Pharmacol. 2024 17 e18761429260902 10.2174/0118761429260902230925044009 38239068
    [Google Scholar]
  5. Sensi B. Angelico R. Toti L. Mechanism, potential, and concerns of immunotherapy for hepatocellular carcinoma and liver transplantation. Curr. Mol. Pharmacol. 2024 17 e18761429310703 10.2174/0118761429310703240823045808 39225204
    [Google Scholar]
  6. Ge G. Jiang X. Tian X. Zhou Y. Cao G. The role of Salvia miltiorrhiza compounds in hepatocellular carcinoma: A preliminary investigation based on computational analysis and liquid chromatography-tandem mass spectrometry. Curr. Pharm. Anal. 2025 21 4 249 264 10.1016/j.cpan.2025.04.001
    [Google Scholar]
  7. Chandarana C.V. Mithani N.T. Singh D.V. Kikani U.B. Vibrational Spectrophotometry: A Comprehensive Review on the Diagnosis of Gastric and Liver Cancer. Curr. Pharm. Anal. 2024 20 7 453 465 10.2174/0115734129322567240821052326
    [Google Scholar]
  8. Ito T. Nguyen M.H. Perspectives on the underlying etiology of HCC and its effects on treatment outcomes. J. Hepatocell. Carcinoma 2023 10 413 428 10.2147/JHC.S347959 36926055
    [Google Scholar]
  9. Lyu N. Wang X. Li J.B. Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: A biomolecular exploratory, randomized, phase III Trial (FOHAIC-1). J. Clin. Oncol. 2022 40 5 468 480 10.1200/JCO.21.01963 34905388
    [Google Scholar]
  10. Zhu H. Shan Y. Ge K. Lu J. Kong W. Jia C. Oxaliplatin induces immunogenic cell death in hepatocellular carcinoma cells and synergizes with immune checkpoint blockade therapy. Cell Oncol. (Dordr.) 2020 43 6 1203 1214 10.1007/s13402‑020‑00552‑2 32797385
    [Google Scholar]
  11. Fan X. Han F. Wang H. YTHDF2-mediated m6A modification of ONECUT2 promotes stemness and oxaliplatin resistance in gastric cancer through transcriptionally activating TFPI. Drug Resist. Updat. 2025 79 101200 10.1016/j.drup.2024.101200 39823826
    [Google Scholar]
  12. Li Q.J. He M.K. Chen H.W. Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: A randomized phase III Trial. J. Clin. Oncol. 2022 40 2 150 160 10.1200/JCO.21.00608 34648352
    [Google Scholar]
  13. Martinez-Balibrea E. Martínez-Cardús A. Ginés A. Tumor-related molecular mechanisms of oxaliplatin resistance. Mol. Cancer Ther. 2015 14 8 1767 1776 10.1158/1535‑7163.MCT‑14‑0636 26184483
    [Google Scholar]
  14. Khanra S. Roychowdhury P. Kuppusamy G. Bhuyan N.R. Ramaswamy S. M R J. Development and validation of an RP-UFLC method for the estimation of oxaliplatin drug for the preparation of oxaliplatin nanoparticles. Curr. Pharm. Anal. 2024 20 8 863 873 10.2174/0115734129329774240829073320
    [Google Scholar]
  15. Haider T. Pandey V. Banjare N. Gupta P.N. Soni V. Drug resistance in cancer: Mechanisms and tackling strategies. Pharmacol. Rep. 2020 72 5 1125 1151 10.1007/s43440‑020‑00138‑7 32700248
    [Google Scholar]
  16. Bukowski K. Kciuk M. Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int. J. Mol. Sci. 2020 21 9 3233 10.3390/ijms21093233 32370233
    [Google Scholar]
  17. Illam S.P. Narayanankutty A. Mathew S.E. Valsalakumari R. Jacob R.M. Raghavamenon A.C. Epithelial mesenchymal transition in cancer progression: prev entive phytochemicals. Recent Patents Anticancer Drug Discov. 2017 12 3 234 246 28440207
    [Google Scholar]
  18. Ma J. Zeng S. Zhang Y. Deng G. Shen H. Epithelial–mesenchymal transition plays a critical role in drug resistance of hepatocellular carcinoma cells to oxaliplatin. Tumour Biol. 2016 37 5 6177 6184 10.1007/s13277‑015‑4458‑z 26614432
    [Google Scholar]
  19. Yang Y. Yao J. Du Q. Connexin 32 downregulation is critical for chemoresistance in oxaliplatin-resistant HCC cells associated with EMT. Cancer Manag. Res. 2019 11 5133 5146 10.2147/CMAR.S203656 31213923
    [Google Scholar]
  20. Chen T. You Y. Jiang H. Wang Z.Z. Epithelial–mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J. Cell. Physiol. 2017 232 12 3261 3272 10.1002/jcp.25797 28079253
    [Google Scholar]
  21. Xu Z. Zhang Y. Dai H. Han B. Epithelial–Mesenchymal transition-mediated tumor therapeutic resistance. Molecules 2022 27 15 4750 10.3390/molecules27154750 35897925
    [Google Scholar]
  22. Garry G. Elisabeth H. Epithelia suspended in collagen gels can lose characteristics of 0migrating mesenchymal cells. J. Cell Biol. 1982 95 333 339 10.1083/jcb.95.1.333 7142291
    [Google Scholar]
  23. Mittal V. Epithelial mesenchymal transition in tumor metastasis. Annu. Rev. Pathol. 2018 13 1 395 412 10.1146/annurev‑pathol‑020117‑043854 29414248
    [Google Scholar]
  24. Lamouille S. Xu J. Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol. 2014 15 3 178 196 10.1038/nrm3758 24556840
    [Google Scholar]
  25. Hariri A. Mirian M. Khosravi A. Zarepour A. Iravani S. Zarrabi A. Intersecting pathways: The role of hybrid E/M cells and circulating tumor cells in cancer metastasis and drug resistance. Drug Resist. Updat. 2024 76 101119 10.1016/j.drup.2024.101119 39111134
    [Google Scholar]
  26. Xiong X.X. Qiu X.Y. Hu D.X. Chen X.Q. Advances in hypoxia-mediated mechanisms in hepatocellular carcinoma. Mol. Pharmacol. 2017 92 3 246 255 10.1124/mol.116.107706 28242743
    [Google Scholar]
  27. Poon E. Harris A.L. Ashcroft M. Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Rev. Mol. Med. 2009 11 e26 10.1017/S1462399409001173 19709449
    [Google Scholar]
  28. Ullah A. Shehzadi S. Ullah N. Hypoxia A typical target in human lung cancer therapy. Curr. Protein Pept. Sci. 2024 25 5 376 385 10.2174/0113892037252820231114045234 38031268
    [Google Scholar]
  29. Bao M.H.R. Wong C.C.L. Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer. Cells 2021 10 7 1715 10.3390/cells10071715 34359884
    [Google Scholar]
  30. Erin N. Grahovac J. Brozovic A. Efferth T. Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Drug Resist. Updat. 2020 53 100715 10.1016/j.drup.2020.100715 32679188
    [Google Scholar]
  31. Hapke R.Y. Haake S.M. Hypoxia-induced epithelial to mesenchymal transition in cancer. Cancer Lett. 2020 487 10 20 10.1016/j.canlet.2020.05.012 32470488
    [Google Scholar]
  32. Tam S.Y. Wu V.W.C. Law H.K.W. Hypoxia-induced epithelial-mesenchymal transition in cancers: HIF-1α and beyond. Front. Oncol. 2020 10 486 10.3389/fonc.2020.00486 32322559
    [Google Scholar]
  33. Lin Y.T. Wu K.J. Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling. J. Biomed. Sci. 2020 27 1 39 10.1186/s12929‑020‑00632‑3 32114978
    [Google Scholar]
  34. Yang F. Sun L. Li Q. SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities. EMBO J. 2012 31 1 110 123 10.1038/emboj.2011.364 21983900
    [Google Scholar]
  35. Yang M.H. Wu M.Z. Chiou S.H. Direct regulation of TWIST by HIF-1α promotes metastasis. Nat. Cell Biol. 2008 10 3 295 305 10.1038/ncb1691 18297062
    [Google Scholar]
  36. Bartel D.P. MicroRNAs. Cell 2004 116 2 281 297 10.1016/S0092‑8674(04)00045‑5 14744438
    [Google Scholar]
  37. Si W. Shen J. Zheng H. Fan W. The role and mechanisms of action of microRNAs in cancer drug resistance. Clin. Epigenetics 2019 11 1 25 10.1186/s13148‑018‑0587‑8 30744689
    [Google Scholar]
  38. Xu X. Tao Y. Shan L. The role of MicroRNAs in hepatocellular carcinoma. J. Cancer 2018 9 19 3557 3569 10.7150/jca.26350 30310513
    [Google Scholar]
  39. Zhang B. Pan X. Cobb G.P. Anderson T.A. microRNAs as oncogenes and tumor suppressors. Dev. Biol. 2007 302 1 1 12 10.1016/j.ydbio.2006.08.028 16989803
    [Google Scholar]
  40. Wei L. Wang X. Lv L. The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma. Mol. Cancer 2019 18 1 147 10.1186/s12943‑019‑1086‑z 31651347
    [Google Scholar]
  41. Konoshenko M. Lansukhay Y. Krasilnikov S. Laktionov P. MicroRNAs as predictors of lung-cancer resistance and sensitivity to cisplatin. Int. J. Mol. Sci. 2022 23 14 7594 10.3390/ijms23147594 35886942
    [Google Scholar]
  42. Dehghanzadeh R. Jadidi-Niaragh F. Gharibi T. Yousefi M. MicroRNA-induced drug resistance in gastric cancer. Biomed. Pharmacother. 2015 74 191 199 10.1016/j.biopha.2015.08.009 26349984
    [Google Scholar]
  43. Mihanfar A. Fattahi A. Nejabati H.R. MicroRNA‐mediated drug resistance in ovarian cancer. J. Cell. Physiol. 2019 234 4 3180 3191 10.1002/jcp.26060 28628227
    [Google Scholar]
  44. Pouya F.D. Gazouli M. Rasmi Y. Lampropoulou D.I. Nemati M. MicroRNAs and drug resistance in colorectal cancer with special focus on 5-fluorouracil. Mol. Biol. Rep. 2022 49 6 5165 5178 10.1007/s11033‑022‑07227‑1 35212928
    [Google Scholar]
  45. Wang J. Yang M. Li Y. Han B. The Role of MicroRNAs in the Chemoresistance of Breast Cancer. Drug Dev. Res. 2015 76 7 368 374 10.1002/ddr.21275 26310899
    [Google Scholar]
  46. Huang W. Hu X. He X. TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770–5p axis in PDAC. Drug Resist. Updat. 2024 74 101079 10.1016/j.drup.2024.101079 38518727
    [Google Scholar]
  47. Zhang Y. Wang J. MicroRNAs are important regulators of drug resistance in colorectal cancer. Biol. Chem. 2017 398 8 929 938 10.1515/hsz‑2016‑0308 28095367
    [Google Scholar]
  48. Gao H.X. Yan L. Li C. Zhao L.M. Liu W. miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1. Mol. Med. Rep. 2016 14 5 4135 4143 10.3892/mmr.2016.5770 27666124
    [Google Scholar]
  49. Wang H.Y. Liu Y.N. Wu S.G. MiR-200c-3p suppression is associated with development of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer via a mediating epithelial-to-mesenchymal transition (EMT) process. Cancer Biomark. 2020 28 3 351 363 10.3233/CBM‑191119 32417760
    [Google Scholar]
  50. Zhu X. Shen H. Yin X. miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin. Oncogene 2016 35 3 323 332 10.1038/onc.2015.84 25867064
    [Google Scholar]
  51. Wang R. Li Y. Hou Y. The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells. Oncotarget 2015 6 9 7000 7010 10.18632/oncotarget.3193 25760076
    [Google Scholar]
  52. Zhang T. Liu W. Zeng X. Down-regulation of microRNA-338-3p promoted angiogenesis in hepatocellular carcinoma. Biomed. Pharmacother. 2016 84 583 591 10.1016/j.biopha.2016.09.056 27694002
    [Google Scholar]
  53. Xu Z. Sun Y. Wang D. Sun H. Liu X. SNHG16 promotes tumorigenesis and cisplatin resistance by regulating miR-338-3p/PLK4 pathway in neuroblastoma cells. Cancer Cell Int. 2020 20 1 236 10.1186/s12935‑020‑01291‑y 32536824
    [Google Scholar]
  54. Lu H. Zhang Q. Sun Y. Wu D. Liu L. LINC00689 induces gastric cancer progression via modulating the miR‐338‐3p/HOXA3 axis. J. Gene Med. 2020 22 12 e3275 10.1002/jgm.3275 32926751
    [Google Scholar]
  55. Zhang P. Shao G. Lin X. Liu Y. Yang Z. Erratum: MiR-338-3p inhibits the growth and invasion of non-small cell lung cancer cells by targeting IRS2. Am. J. Cancer Res. 2021 11 8 4002 4004 34522464
    [Google Scholar]
  56. Saxena M. Stephens M.A. Pathak H. Rangarajan A. Transcription factors that mediate epithelial–mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis. 2011 2 7 e179 10.1038/cddis.2011.61 21734725
    [Google Scholar]
  57. Jang J.Y. Kim M.K. Jeon Y.K. Joung Y.K. Park K.D. Kim C.W. Adenovirus adenine nucleotide translocator-2 shRNA effectively induces apoptosis and enhances chemosensitivity by the down-regulation of ABCG2 in breast cancer stem-like cells. Exp. Mol. Med. 2012 44 4 251 259 10.3858/emm.2012.44.4.019 22198296
    [Google Scholar]
  58. Li L. Jiang A.C. Dong P. Wang H. Xu W. Xu C. MDR1/P-gp and VEGF synergistically enhance the invasion of Hep-2 cells with multidrug resistance induced by taxol. Ann. Surg. Oncol. 2009 16 5 1421 1428 10.1245/s10434‑009‑0395‑7 19247716
    [Google Scholar]
  59. Shibue T. Weinberg R.A. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat. Rev. Clin. Oncol. 2017 14 10 611 629 10.1038/nrclinonc.2017.44 28397828
    [Google Scholar]
  60. Diehn M. Cho R.W. Lobo N.A. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009 458 7239 780 783 10.1038/nature07733 19194462
    [Google Scholar]
  61. Zhou P. Ye M. Chen C. Zhang R. Adhesin component member STAG2 enhances cisplatin tolerance in colorectal cancer cells through the epithelial-mesenchymal transition pathway. Recent Patents Anticancer Drug Discov. 2024 2 19 38963118
    [Google Scholar]
  62. Ao J. Chiba T. Shibata S. Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells. Biochem. Biophys. Res. Commun. 2021 549 171 178 10.1016/j.bbrc.2021.02.097 33676186
    [Google Scholar]
  63. Zhang Y. Huang S. Up-regulation of miR-125b reverses epithelial-mesenchymal transition in paclitaxel-resistant lung cancer cells. Biol. Chem. 2015
    [Google Scholar]
  64. Diepenbruck M. Christofori G. Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr. Opin. Cell Biol. 2016 43 7 13 10.1016/j.ceb.2016.06.002 27371787
    [Google Scholar]
  65. Pan G. Liu Y. Shang L. Zhou F. Yang S. EMT‐associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun. (Lond.) 2021 41 3 199 217 10.1002/cac2.12138 33506604
    [Google Scholar]
  66. Wang T. Dong W. Wang F. Downregulation of miRNA-14669 Reverses Vincristine Resistance in Colorectal Cancer Cells through PI3K/AKT Signaling Pathway. Recent Patents Anticancer Drug Discov. 2022 17 2 178 186 10.2174/1574892816666210806154225 34365931
    [Google Scholar]
  67. Zhang J. Yang W. Xiao Y. Shan L. MiR-125b inhibits cell proliferation and induces apoptosis in human colon cancer SW480 cells via targeting STAT3. Recent Patents Anticancer Drug Discov. 2022 17 2 187 194 10.2174/1574892816666210708165037 34238196
    [Google Scholar]
  68. Liu Q. Zhu C. Dong Y. LncRNA TCTN2 promotes the malignant development of hepatocellular carcinoma via regulating mIR-1285-3p/ARF6 Axis. Recent Patents Anticancer Drug Discov. 2023 18 4 517 527 10.2174/1574892818666221019163656 36278455
    [Google Scholar]
  69. Tao L. Shu-Ling W. Jing-Bo H. MiR-451a attenuates doxorubicin resistance in lung cancer via suppressing epithelialmesenchymal transition (EMT) through targeting c-Myc. Biomed. Pharmacother. 2020 125 109962 10.1016/j.biopha.2020.109962 32106373
    [Google Scholar]
  70. Zhang J. Hua X. Qi N. MiR-27b suppresses epithelial–mesenchymal transition and chemoresistance in lung cancer by targeting Snail1. Life Sci. 2020 254 117238 10.1016/j.lfs.2019.117238 31887300
    [Google Scholar]
  71. Chen Y. Zhao X.H. Zhang D.D. Zhao Y. MiR-513a-3p inhibits EMT mediated by HOXB7 and promotes sensitivity to cisplatin in ovarian cancer cells. Eur. Rev. Med. Pharmacol. Sci. 2020 24 20 10391 10402 33155195
    [Google Scholar]
  72. Yang J. Hai J. Dong X. Zhang M. Duan S. MicroRNA-92a-3p enhances cisplatin resistance by regulating krüppel-like factor 4-mediated cell apoptosis and epithelial-to-mesenchymal transition in cervical cancer. Front. Pharmacol. 2022 12 783213 10.3389/fphar.2021.783213 35095494
    [Google Scholar]
  73. Wang M. Zhang R. Zhang S. Xu R. Yang Q. MicroRNA-574-3p regulates epithelial mesenchymal transition and cisplatin resistance via targeting ZEB1 in human gastric carcinoma cells. Gene 2019 700 110 119 10.1016/j.gene.2019.03.043 30917930
    [Google Scholar]
  74. Chen Y. Wang L. Zhou J. Effects of microRNA‐1271 on ovarian cancer via inhibition of epithelial‐mesenchymal transition and cisplatin resistance. J. Obstet. Gynaecol. Res. 2019 45 11 2243 2254 10.1111/jog.14079 31411791
    [Google Scholar]
  75. Tang Q. Wen H. Hu H. Circ_0070203 promotes epithelial-mesenchymal transition in ovarian serous cystadenocarcinoma through miR-370-3p/TGFβR2 Axis. Recent Patents Anticancer Drug Discov. 2024 19 2 233 246 10.2174/1574892818666230328124804 38214360
    [Google Scholar]
  76. Liu Y. Li Y. Wang R. MiR-130a-3p regulates cell migration and invasion via inhibition of Smad4 in gemcitabine resistant hepatoma cells. J. Exp. Clin. Cancer Res. 2016 35 1 19 10.1186/s13046‑016‑0296‑0 26817584
    [Google Scholar]
  77. Shao Q. Zhang P. Ma Y. MicroRNA-139-5p affects cisplatin sensitivity in human nasopharyngeal carcinoma cells by regulating the epithelial-to-mesenchymal transition. Gene 2018 652 48 58 10.1016/j.gene.2018.02.003 29427737
    [Google Scholar]
  78. Brozovic A. Duran G.E. Wang Y.C. Francisco E.B. Sikic B.I. The miR‐200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR‐3 and MES‐OV cells. Mol. Oncol. 2015 9 8 1678 1693 10.1016/j.molonc.2015.04.015 26025631
    [Google Scholar]
  79. Chen J.S. Liang L.L. Xu H.X. miR-338-3p inhibits epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma cells. Oncotarget 2017 8 42 71418 71429 10.18632/oncotarget.10138 29069716
    [Google Scholar]
  80. Minassian L.M. Cotechini T. Huitema E. Graham C.H. Hypoxia-Induced Resistance to Chemotherapy in Cancer. Adv. Exp. Med. Biol. 2019 1136 123 139 10.1007/978‑3‑030‑12734‑3_9 31201721
    [Google Scholar]
  81. Jiao M. Nan K.J. Activation of PI3 kinase/Akt/HIF-1α pathway contributes to hypoxia-induced epithelial-mesenchymal transition and chemoresistance in hepatocellular carcinoma. Int. J. Oncol. 2012 40 2 461 468 21922131
    [Google Scholar]
  82. Chai D. Bao Z. Hu J. Ma L. Feng Z. Tao Y. Vasculogenic mimicry and aberrant expression of HIF-lα/E-cad are associated with worse prognosis of esophageal squamous cell carcinoma. J. Huazhong Univ. Sci. Technolog. Med. Sci. 2013 33 3 385 391 10.1007/s11596‑013‑1129‑4 23771665
    [Google Scholar]
  83. Xu H. Zhao L. Fang Q. MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α. PLoS One 2014 9 12 e115565 10.1371/journal.pone.0115565 25531114
    [Google Scholar]
  84. Shan Y. Li X. You B. Shi S. Zhang Q. You Y. MicroRNA-338 inhibits migration and proliferation by targeting hypoxia-induced factor 1α in nasopharyngeal carcinoma. Oncol. Rep. 2015 34 4 1943 1952 10.3892/or.2015.4195 26260688
    [Google Scholar]
  85. Qian W. Huang T. Feng W. Circular RNA HIPK3 promotes EMT of cervical cancer through sponging miR-338-3p to Up-Regulate HIF-1α. Cancer Manag. Res. 2020 12 177 187 10.2147/CMAR.S232235 32021434
    [Google Scholar]
  86. Zhang X.D. Dong X.Q. Xu J.L. Chen S.C. Sun Z. Hypoxia promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells via inducing Twist1 expression. Eur. Rev. Med. Pharmacol. Sci. 2017 21 13 3061 3068 28742200
    [Google Scholar]
  87. Yang M.H. Wu K.J. TWIST activation by hypoxia inducible factor-1 (HIF-1): Implications in metastasis and development. Cell Cycle 2008 7 14 2090 2096 10.4161/cc.7.14.6324 18635960
    [Google Scholar]
/content/journals/pra/10.2174/0115748928408751251113182005
Loading
Mir-338-3p Increases the Sensitivity to Oxaliplatin via Reversing Epithelial-mesenchymal Transition in Hepatocellular Carcinoma Cells
Bentham Science Publishers ; https://doi.org/10.2174/0115748928408751251113182005
/content/journals/pra/10.2174/0115748928408751251113182005
/content/journals/pra/10.2174/0115748928408751251113182005
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: OXA-resistance ; TWIST ; HCC ; EMT ; HIF-1α ; miR-338-3p

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test