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Article

Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma

  • Authors:
    • Ai-Qing Lu
    • Bin Lv
    • Fei Qiu
    • Xiao-Yun Wang
    • Xiao-Hua Cao
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasound, The First People's Hospital of Jining, Jining, Shandong 272100, P.R. China, Department of Gastrointestinal Surgery, The First People's Hospital of Jining, Jining, Shandong 272100, P.R. China, Neonatal Intensive Care Unit, The First People's Hospital of Jining, Jining, Shandong 272100, P.R. China, The First Intensive Care Unit, The First People's Hospital of Jining, Jining, Shandong 272100, P.R. China
  • Pages: 2071-2078
    |
    Published online on: March 10, 2017
       https://doi.org/10.3892/or.2017.5498
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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. More than 80% of patients with HCC are not good candidates for curative surgical resection due to advanced liver cirrhosis caused by underlying chronic hepatitis virus (B or C) infection. Sorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced HCC. Although, sorafenib currently sets the new standard for advanced HCC treatment, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical. In the present study, we found that adenine nucleotide translocator 2 (ANT2) was upregulated in sorafenib‑resistant HCC Huh7 cells (Huh7-R) and its overexpression promoted sorafenib resistance. ANT2 induced the formation of cancer-initiating cell (CIC) phenotypes and promoted metastasis-associated traits in the Huh7 cells. Silencing of miR-137 upregulated ANT2 protein expression in the Huh7 cells. miR-137 was downregulated in the Huh7-R cells, compared with that in the Huh7 cells and its restoration reversed sorafenib resistance in the Huh7-R cells. Restoration of miR-137 inhibited formation of CIC traits and attenuated the abilities of migration and invasion in the Huh7-R cells. Moreover, we demonstrated that high-intensity focused ultrasound (HIFU) in unresectable HCC upregulated serum miR-137. Combining HIFU and sorafenib may be a wise option for advanced and unresectable HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Lu A, Lv B, Qiu F, Wang X and Cao X: Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma. Oncol Rep 37: 2071-2078, 2017.
APA
Lu, A., Lv, B., Qiu, F., Wang, X., & Cao, X. (2017). Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma. Oncology Reports, 37, 2071-2078. https://doi.org/10.3892/or.2017.5498
MLA
Lu, A., Lv, B., Qiu, F., Wang, X., Cao, X."Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma". Oncology Reports 37.4 (2017): 2071-2078.
Chicago
Lu, A., Lv, B., Qiu, F., Wang, X., Cao, X."Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma". Oncology Reports 37, no. 4 (2017): 2071-2078. https://doi.org/10.3892/or.2017.5498
Copy and paste a formatted citation
x
Spandidos Publications style
Lu A, Lv B, Qiu F, Wang X and Cao X: Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma. Oncol Rep 37: 2071-2078, 2017.
APA
Lu, A., Lv, B., Qiu, F., Wang, X., & Cao, X. (2017). Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma. Oncology Reports, 37, 2071-2078. https://doi.org/10.3892/or.2017.5498
MLA
Lu, A., Lv, B., Qiu, F., Wang, X., Cao, X."Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma". Oncology Reports 37.4 (2017): 2071-2078.
Chicago
Lu, A., Lv, B., Qiu, F., Wang, X., Cao, X."Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma". Oncology Reports 37, no. 4 (2017): 2071-2078. https://doi.org/10.3892/or.2017.5498
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