Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma
| Autor: | Fei Qiu, Xiao-Yun Wang, Bin Lv, Xiao-Hua Cao, Ai-Qing Lu |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Niacinamide 0301 basic medicine Oncology Sorafenib Cancer Research medicine.medical_specialty Carcinoma Hepatocellular Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Internal medicine medicine Carcinoma Humans 3' Untranslated Regions neoplasms Oncogene Phenylurea Compounds Liver Neoplasms Cancer Adenine Nucleotide Translocator 2 Hep G2 Cells General Medicine Cell cycle medicine.disease Molecular medicine digestive system diseases Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs mir-137 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Hepatocellular carcinoma Neoplastic Stem Cells Cancer research High-Intensity Focused Ultrasound Ablation Female medicine.drug |
| Zdroj: | Oncology Reports. 37:2071-2078 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2017.5498 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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