Hepatitis B virus X protein boosts hepatocellular carcinoma progression by downregulating microRNA-137
Copyright © 2020 Elsevier GmbH. All rights reserved..
BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent diagnosed malignancy. microRNAs (miRs) are involved in various cellular processes during cancer development. This study attempted to probe the miR-based mechanism in hepatitis B virus X protein (HBx) small interfering RNA (siRNA)-treated HCC cells.
METHODS: HBx expression in hepatocyte and HCC cells was detected, and cells with highest HBx expression were screened out and transfected with HBx-siRNAs. Then the effect of HBx on HCC cell proliferation was detected. miRs differentially expressed in HBx-siRNA-transfected MHCC97H cells were analyzed and verified. miR-137 methylation was analyzed by bioinformatics, and miR-137 restoration was detected after Aza treatment. Furthermore, miR-137 methylation in MHCC97H cells with HBx knockdown or HBx overexpression was detected by methylation specific PCR. The targeting relationship between miR-137 and Notch1 was verified. Then the gain-and-loss functions of miR-137 or/and Notch1 were performed to estimate their roles in HCC cell proliferation. The effects of HBx-siRNA and overexpressed miR-137 in vivo were observed by tumor xenograft in nude mice and immunohistochemistry.
RESULTS: HBx-siRNA weakened MHCC97H cell proliferation and tumor growth. miR-137 was highly expressed in HBx-siRNA-treated HCC cells and targeted Notch1. HBx knockdown decreased miR-137 methylation and restored miR-137 expression. miR-137 overexpression prevented HCC cell proliferation and tumor growth, while miR-137 downregulation reversed the repressing effects of HBx-siRNA on HCC cell proliferation. Inhibition of Notch1 reversed HCC cell proliferation induced by miR-137 downregulation.
CONCLUSION: Overexpression of miR-137 blocks HCC cell proliferation in HBx-siRNA-treated MHCC97H cells by targeting Notch1. This study may offer novel target for HCC treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:216 |
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| Enthalten in: |
Pathology, research and practice - 216(2020), 6 vom: 16. Juni, Seite 152981 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Yong [VerfasserIn] |
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| Links: |
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| Themen: |
Hepatitis B virus X protein |
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| Anmerkungen: |
Date Completed 01.04.2021 Date Revised 01.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.prp.2020.152981 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31106664X |
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| 500 | |a Date Revised 01.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier GmbH. All rights reserved. | ||
| 520 | |a BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent diagnosed malignancy. microRNAs (miRs) are involved in various cellular processes during cancer development. This study attempted to probe the miR-based mechanism in hepatitis B virus X protein (HBx) small interfering RNA (siRNA)-treated HCC cells | ||
| 520 | |a METHODS: HBx expression in hepatocyte and HCC cells was detected, and cells with highest HBx expression were screened out and transfected with HBx-siRNAs. Then the effect of HBx on HCC cell proliferation was detected. miRs differentially expressed in HBx-siRNA-transfected MHCC97H cells were analyzed and verified. miR-137 methylation was analyzed by bioinformatics, and miR-137 restoration was detected after Aza treatment. Furthermore, miR-137 methylation in MHCC97H cells with HBx knockdown or HBx overexpression was detected by methylation specific PCR. The targeting relationship between miR-137 and Notch1 was verified. Then the gain-and-loss functions of miR-137 or/and Notch1 were performed to estimate their roles in HCC cell proliferation. The effects of HBx-siRNA and overexpressed miR-137 in vivo were observed by tumor xenograft in nude mice and immunohistochemistry | ||
| 520 | |a RESULTS: HBx-siRNA weakened MHCC97H cell proliferation and tumor growth. miR-137 was highly expressed in HBx-siRNA-treated HCC cells and targeted Notch1. HBx knockdown decreased miR-137 methylation and restored miR-137 expression. miR-137 overexpression prevented HCC cell proliferation and tumor growth, while miR-137 downregulation reversed the repressing effects of HBx-siRNA on HCC cell proliferation. Inhibition of Notch1 reversed HCC cell proliferation induced by miR-137 downregulation | ||
| 520 | |a CONCLUSION: Overexpression of miR-137 blocks HCC cell proliferation in HBx-siRNA-treated MHCC97H cells by targeting Notch1. This study may offer novel target for HCC treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatitis B virus X protein | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Methylation | |
| 650 | 4 | |a Notch1 | |
| 650 | 4 | |a microRNA-137 | |
| 650 | 7 | |a MIRN137 microRNA, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Trans-Activators |2 NLM | |
| 650 | 7 | |a Viral Regulatory and Accessory Proteins |2 NLM | |
| 650 | 7 | |a hepatitis B virus X protein |2 NLM | |
| 700 | 1 | |a Gu, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yueping |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Decai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wensheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Guofu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xuedong |e verfasserin |4 aut | |
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