Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway
Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor. It has been found that autophagy plays a role both as a tumor promoter and inhibitor in HCC carcinogenesis. However, the mechanism behind is still unveiled. This study aims to explore the functions and mechanism of the key autoph...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/5/906 |
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| author | Jiahao Li Lansi Chen Jingjing Pang Chunxiu Yang Wen Xie Guoyan Shen Hongshan Chen Xiaoyi Li Shu-Yuan Xiao Yueying Li |
| author_facet | Jiahao Li Lansi Chen Jingjing Pang Chunxiu Yang Wen Xie Guoyan Shen Hongshan Chen Xiaoyi Li Shu-Yuan Xiao Yueying Li |
| author_sort | Jiahao Li |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor. It has been found that autophagy plays a role both as a tumor promoter and inhibitor in HCC carcinogenesis. However, the mechanism behind is still unveiled. This study aims to explore the functions and mechanism of the key autophagy-related proteins, to shed light on novel clinical diagnoses and treatment targets of HCC. Bioinformation analyses were performed by using data from public databases including TCGA, ICGC, and UCSC Xena. The upregulated autophagy-related gene WDR45B was identified and validated in human liver cell line LO2, human HCC cell line HepG2 and Huh-7. Immunohistochemical assay (IHC) was also performed on formalin-fixed paraffin-embedded (FFPE) tissues of 56 HCC patients from our pathology archives. By using qRT-PCR and Western blots we found that high expression of WDR45B influenced the Akt/mTOR signaling pathway. Autophagy marker LC3- II/LC3-I was downregulated, and p62/SQSTM1 was upregulated after knockdown of WDR45B. The effects of WDR45B knockdown on autophagy and Akt/mTOR signaling pathways can be reversed by the autophagy inducer rapamycin. Moreover, proliferation and migration of HCC can be inhibited after the knockdown of WDR45B through the CCK8 assay, wound-healing assay and Transwell cell migration and invasion assay. Therefore, WDR45B may become a novel biomarker for HCC prognosis assessment and potential target for molecular therapy. |
| first_indexed | 2024-03-11T07:27:48Z |
| format | Article |
| id | doaj.art-9c6c2a35b4ce4e9e95a74c6b757039c2 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T07:27:48Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-9c6c2a35b4ce4e9e95a74c6b757039c22023-11-17T07:29:48ZengMDPI AGDiagnostics2075-44182023-02-0113590610.3390/diagnostics13050906Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling PathwayJiahao Li0Lansi Chen1Jingjing Pang2Chunxiu Yang3Wen Xie4Guoyan Shen5Hongshan Chen6Xiaoyi Li7Shu-Yuan Xiao8Yueying Li9Department of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaDepartment of Pathology, Jiahui International Hospital, Shanghai 200000, ChinaDepartment of Pathology, Wuhan University Zhongnan Hospital, Wuhan 430071, ChinaHepatocellular carcinoma (HCC) is a highly aggressive malignant tumor. It has been found that autophagy plays a role both as a tumor promoter and inhibitor in HCC carcinogenesis. However, the mechanism behind is still unveiled. This study aims to explore the functions and mechanism of the key autophagy-related proteins, to shed light on novel clinical diagnoses and treatment targets of HCC. Bioinformation analyses were performed by using data from public databases including TCGA, ICGC, and UCSC Xena. The upregulated autophagy-related gene WDR45B was identified and validated in human liver cell line LO2, human HCC cell line HepG2 and Huh-7. Immunohistochemical assay (IHC) was also performed on formalin-fixed paraffin-embedded (FFPE) tissues of 56 HCC patients from our pathology archives. By using qRT-PCR and Western blots we found that high expression of WDR45B influenced the Akt/mTOR signaling pathway. Autophagy marker LC3- II/LC3-I was downregulated, and p62/SQSTM1 was upregulated after knockdown of WDR45B. The effects of WDR45B knockdown on autophagy and Akt/mTOR signaling pathways can be reversed by the autophagy inducer rapamycin. Moreover, proliferation and migration of HCC can be inhibited after the knockdown of WDR45B through the CCK8 assay, wound-healing assay and Transwell cell migration and invasion assay. Therefore, WDR45B may become a novel biomarker for HCC prognosis assessment and potential target for molecular therapy.https://www.mdpi.com/2075-4418/13/5/906hepatocellular carcinomaautophagyprognosisWDR45BAkt/mTOR signaling pathway |
| spellingShingle | Jiahao Li Lansi Chen Jingjing Pang Chunxiu Yang Wen Xie Guoyan Shen Hongshan Chen Xiaoyi Li Shu-Yuan Xiao Yueying Li Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway Diagnostics hepatocellular carcinoma autophagy prognosis WDR45B Akt/mTOR signaling pathway |
| title | Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway |
| title_full | Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway |
| title_fullStr | Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway |
| title_full_unstemmed | Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway |
| title_short | Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway |
| title_sort | autophagy related gene wd repeat domain 45b promotes tumor proliferation and migration of hepatocellular carcinoma through the akt mtor signaling pathway |
| topic | hepatocellular carcinoma autophagy prognosis WDR45B Akt/mTOR signaling pathway |
| url | https://www.mdpi.com/2075-4418/13/5/906 |
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