MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling
Abstract Previous studies have indicated that Zinc ribbon domain‐containing 1 (ZNRD1) is attributed to the carcinogenesis of human tumors. However, the role of ZNRD1 and its regulation in hepatocellular carcinoma (HCC) are still largely unclear. In this study, we examined the expression profiles of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2613 |
| _version_ | 1828779805690036224 |
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| author | Xiaobo Hu Ruifang Wang Zhigang Ren Xiaorui Liu Junsheng Gu Guangying Cui Qinggang Li |
| author_facet | Xiaobo Hu Ruifang Wang Zhigang Ren Xiaorui Liu Junsheng Gu Guangying Cui Qinggang Li |
| author_sort | Xiaobo Hu |
| collection | DOAJ |
| description | Abstract Previous studies have indicated that Zinc ribbon domain‐containing 1 (ZNRD1) is attributed to the carcinogenesis of human tumors. However, the role of ZNRD1 and its regulation in hepatocellular carcinoma (HCC) are still largely unclear. In this study, we examined the expression profiles of ZNRD1 in HCC tissues by immunohistochemistry (IHC) and publicly datasets analysis. In vitro and in vivo experiments were conducted to identify the function of ZNRD1 in HCC. In addition, miRNA potentially targeting ZNRD1 was predicted by bioinformatics analysis and further verified via in vitro experiments. Our results revealed that ZNRD1 was frequently upregulated in HCC tissues compared with that in nontumor tissues. High ZNRD1 expression in HCC tissues was positively associated with advanced tumor stage and poor prognosis. Function experiments showed that knockdown of ZNRD1 inhibited cell growth and invasion in vitro, and suppressed tumor development in vivo. Moreover, ZNRD1 promoted the activation of Wnt/β‐catenin signaling pathway in HCC. Importantly, miR‐26b directly inhibited the transcription activity of ZNRD1. Overexpression of ZNRD1 dramatically abolished the inhibitory effects of miR‐26b on HCC cells. Taken together, our results uncover a novel mechanistic role for miR‐26b/ZNRD1 axis in HCC, proposing ZNRD1 inhibition as a potent therapeutic strategy for hepatocellular carcinoma. |
| first_indexed | 2024-12-11T17:07:40Z |
| format | Article |
| id | doaj.art-a785330adff6404ba66f3cd8b5f93787 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-11T17:07:40Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-a785330adff6404ba66f3cd8b5f937872022-12-22T00:57:38ZengWileyCancer Medicine2045-76342019-12-018177359737110.1002/cam4.2613MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signalingXiaobo Hu0Ruifang Wang1Zhigang Ren2Xiaorui Liu3Junsheng Gu4Guangying Cui5Qinggang Li6Department of Infectious Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Nuclear Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Infectious Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Infectious Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Infectious Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Infectious Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Infectious Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaAbstract Previous studies have indicated that Zinc ribbon domain‐containing 1 (ZNRD1) is attributed to the carcinogenesis of human tumors. However, the role of ZNRD1 and its regulation in hepatocellular carcinoma (HCC) are still largely unclear. In this study, we examined the expression profiles of ZNRD1 in HCC tissues by immunohistochemistry (IHC) and publicly datasets analysis. In vitro and in vivo experiments were conducted to identify the function of ZNRD1 in HCC. In addition, miRNA potentially targeting ZNRD1 was predicted by bioinformatics analysis and further verified via in vitro experiments. Our results revealed that ZNRD1 was frequently upregulated in HCC tissues compared with that in nontumor tissues. High ZNRD1 expression in HCC tissues was positively associated with advanced tumor stage and poor prognosis. Function experiments showed that knockdown of ZNRD1 inhibited cell growth and invasion in vitro, and suppressed tumor development in vivo. Moreover, ZNRD1 promoted the activation of Wnt/β‐catenin signaling pathway in HCC. Importantly, miR‐26b directly inhibited the transcription activity of ZNRD1. Overexpression of ZNRD1 dramatically abolished the inhibitory effects of miR‐26b on HCC cells. Taken together, our results uncover a novel mechanistic role for miR‐26b/ZNRD1 axis in HCC, proposing ZNRD1 inhibition as a potent therapeutic strategy for hepatocellular carcinoma.https://doi.org/10.1002/cam4.2613HCCmiR‐26bWnt/β‐catenin signaling pathwayZNRD1 |
| spellingShingle | Xiaobo Hu Ruifang Wang Zhigang Ren Xiaorui Liu Junsheng Gu Guangying Cui Qinggang Li MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling Cancer Medicine HCC miR‐26b Wnt/β‐catenin signaling pathway ZNRD1 |
| title | MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling |
| title_full | MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling |
| title_fullStr | MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling |
| title_full_unstemmed | MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling |
| title_short | MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling |
| title_sort | mir 26b suppresses hepatocellular carcinoma development by negatively regulating znrd1 and wnt β catenin signaling |
| topic | HCC miR‐26b Wnt/β‐catenin signaling pathway ZNRD1 |
| url | https://doi.org/10.1002/cam4.2613 |
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