The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis
Xiang Xu Kong,1,* Xiao Yang,1,* Wang Jie Jiang,1,* De Ming Zhu,1,2 Lian Bao Kong1,2 1Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Me...
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| Format: | Article |
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Dove Medical Press
2023-07-01
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| Series: | Journal of Hepatocellular Carcinoma |
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| Online Access: | https://www.dovepress.com/the-long-non-coding-rna-ac0063291-facilitates-hepatocellular-carcinoma-peer-reviewed-fulltext-article-JHC |
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| author | Kong XX Yang X Jiang WJ Zhu DM Kong LB |
| author_facet | Kong XX Yang X Jiang WJ Zhu DM Kong LB |
| author_sort | Kong XX |
| collection | DOAJ |
| description | Xiang Xu Kong,1,* Xiao Yang,1,* Wang Jie Jiang,1,* De Ming Zhu,1,2 Lian Bao Kong1,2 1Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian Bao Kong, Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China, Tel +86-138-0158-3199, Email lbkong@njmu.edu.cnPurpose: Hepatocellular carcinoma(HCC) is the most common type of liver cancer and the sixth largest common cancer worldwide. Although surgical resection, hepatic arterial chemoembolization, targeted drugs and immunotherapy are currently available, the mortality of advanced patients remains high. Therefore, new therapeutic targets are urgently needed. In recent years, many studies have found that The long non-coding RNA(lncRNA) has multiple functions in human tumors, including participating in epigenetic, transcriptional, post-transcriptional and translational regulation, and is closely related to the progression of HCC. The purpose of this study was to investigate the role of AC006329.1 in HCC progression and provide theoretical guidance for finding new targets.Patients and Methods: AC006329.1 was screened out by transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Then a series of functional tests in vivo and in vitro were conducted to investigate the effects of AC006329.1 on HCC progression and metastasis. Epithelial-mesenchymal transformation (EMT) of HCC was detected by Western blot and immunofluorescence staining. The targeted miRNA and downstream gene of AC006329.1 were predicted by databases and the pathway regulation axis eventually validated by dual luciferase reporter assays, qRT-PCR and WB.Results: AC006329.1 was found high expressed in HCC tissues and cell lines by qRT-PCR. The prognosis of HCC patients with high expressed AC006329.1 was poor. In vitro and in vivo, overexpression of AC006329.1 can promote the progression, metastasis and EMT of HCC by acting as a sponge of miR-127-5p to increase the expression of SHC3. In addition, up-regulation of miR-127-5p or knockdown of SHC3 can both reverse the promoting effects of AC006329.1 on progression, metastasis and EMT of HCC. Finally, WB and qRT-PCR analysis was discovered that AC006329.1 can facilitate HCC progression, EMT and metastasis by competitively inhibiting miR-127-5p to activate SHC3/ERK signaling pathway.Conclusion: These above experimental results confirmed that AC006329.1 can facilitate HCC progression, EMT and metastasis by acting as a competing endogenous RNA (ceRNA) to inhibit miR-127-5p and activate SHC3/ERK signaling pathway.Keywords: AC006329.1, miR-127-5p, SHC3, EMT, HCC |
| first_indexed | 2024-03-12T23:05:47Z |
| format | Article |
| id | doaj.art-85e3665b249c4815a6acae15bef313f0 |
| institution | Directory Open Access Journal |
| issn | 2253-5969 |
| language | English |
| last_indexed | 2024-03-12T23:05:47Z |
| publishDate | 2023-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Hepatocellular Carcinoma |
| spelling | doaj.art-85e3665b249c4815a6acae15bef313f02023-07-18T18:55:21ZengDove Medical PressJournal of Hepatocellular Carcinoma2253-59692023-07-01Volume 101085110385188The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK AxisKong XXYang XJiang WJZhu DMKong LBXiang Xu Kong,1,* Xiao Yang,1,* Wang Jie Jiang,1,* De Ming Zhu,1,2 Lian Bao Kong1,2 1Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian Bao Kong, Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China, Tel +86-138-0158-3199, Email lbkong@njmu.edu.cnPurpose: Hepatocellular carcinoma(HCC) is the most common type of liver cancer and the sixth largest common cancer worldwide. Although surgical resection, hepatic arterial chemoembolization, targeted drugs and immunotherapy are currently available, the mortality of advanced patients remains high. Therefore, new therapeutic targets are urgently needed. In recent years, many studies have found that The long non-coding RNA(lncRNA) has multiple functions in human tumors, including participating in epigenetic, transcriptional, post-transcriptional and translational regulation, and is closely related to the progression of HCC. The purpose of this study was to investigate the role of AC006329.1 in HCC progression and provide theoretical guidance for finding new targets.Patients and Methods: AC006329.1 was screened out by transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Then a series of functional tests in vivo and in vitro were conducted to investigate the effects of AC006329.1 on HCC progression and metastasis. Epithelial-mesenchymal transformation (EMT) of HCC was detected by Western blot and immunofluorescence staining. The targeted miRNA and downstream gene of AC006329.1 were predicted by databases and the pathway regulation axis eventually validated by dual luciferase reporter assays, qRT-PCR and WB.Results: AC006329.1 was found high expressed in HCC tissues and cell lines by qRT-PCR. The prognosis of HCC patients with high expressed AC006329.1 was poor. In vitro and in vivo, overexpression of AC006329.1 can promote the progression, metastasis and EMT of HCC by acting as a sponge of miR-127-5p to increase the expression of SHC3. In addition, up-regulation of miR-127-5p or knockdown of SHC3 can both reverse the promoting effects of AC006329.1 on progression, metastasis and EMT of HCC. Finally, WB and qRT-PCR analysis was discovered that AC006329.1 can facilitate HCC progression, EMT and metastasis by competitively inhibiting miR-127-5p to activate SHC3/ERK signaling pathway.Conclusion: These above experimental results confirmed that AC006329.1 can facilitate HCC progression, EMT and metastasis by acting as a competing endogenous RNA (ceRNA) to inhibit miR-127-5p and activate SHC3/ERK signaling pathway.Keywords: AC006329.1, miR-127-5p, SHC3, EMT, HCChttps://www.dovepress.com/the-long-non-coding-rna-ac0063291-facilitates-hepatocellular-carcinoma-peer-reviewed-fulltext-article-JHCac006329.1mir-127-5pshc3emt，hcc |
| spellingShingle | Kong XX Yang X Jiang WJ Zhu DM Kong LB The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis Journal of Hepatocellular Carcinoma ac006329.1 mir-127-5p shc3 emt，hcc |
| title | The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis |
| title_full | The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis |
| title_fullStr | The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis |
| title_full_unstemmed | The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis |
| title_short | The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis |
| title_sort | long non coding rna ac006329 1 facilitates hepatocellular carcinoma progression and metastasis by regulating mir 127 5p shc3 erk axis |
| topic | ac006329.1 mir-127-5p shc3 emt，hcc |
| url | https://www.dovepress.com/the-long-non-coding-rna-ac0063291-facilitates-hepatocellular-carcinoma-peer-reviewed-fulltext-article-JHC |
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