Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met
Abstract Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up‐regul...
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| Format: | Article |
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Wiley
2020-03-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12156 |
| _version_ | 1811212804359716864 |
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| author | Jia‐Jie Chen Xu Sun Qi‐Qi Mao Xiao‐Yun Jiang Xian‐Guang Zhao Wei‐Jia Xu Liang Zhong |
| author_facet | Jia‐Jie Chen Xu Sun Qi‐Qi Mao Xiao‐Yun Jiang Xian‐Guang Zhao Wei‐Jia Xu Liang Zhong |
| author_sort | Jia‐Jie Chen |
| collection | DOAJ |
| description | Abstract Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up‐regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse‐free survival, progression‐ free survival and disease‐specific survival in HCC patients via exploring the Kaplan‐Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over‐expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c‐Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c‐Met; consistently, HN1 over‐expression reversed these effects. Meanwhile, down‐regulation of c‐Met partly eliminated the effect of HN1 over‐expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up‐regulating the expression of c‐Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC. |
| first_indexed | 2024-04-12T05:35:24Z |
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| id | doaj.art-3cb3b3153d92428394592e4e5f32496b |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-04-12T05:35:24Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-3cb3b3153d92428394592e4e5f32496b2022-12-22T03:45:51ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502020-03-0136319620510.1002/kjm2.12156Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐MetJia‐Jie Chen0Xu Sun1Qi‐Qi Mao2Xiao‐Yun Jiang3Xian‐Guang Zhao4Wei‐Jia Xu5Liang Zhong6Department of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaDepartment of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaDepartment of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaDepartment of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaDepartment of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaDepartment of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaDepartment of Gastroenterology Huashan Hospital North, Fudan University Shanghai ChinaAbstract Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up‐regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse‐free survival, progression‐ free survival and disease‐specific survival in HCC patients via exploring the Kaplan‐Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over‐expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c‐Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c‐Met; consistently, HN1 over‐expression reversed these effects. Meanwhile, down‐regulation of c‐Met partly eliminated the effect of HN1 over‐expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up‐regulating the expression of c‐Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC.https://doi.org/10.1002/kjm2.12156HepatocellularcarcinomaHN1c‐Metprognosis |
| spellingShingle | Jia‐Jie Chen Xu Sun Qi‐Qi Mao Xiao‐Yun Jiang Xian‐Guang Zhao Wei‐Jia Xu Liang Zhong Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met Kaohsiung Journal of Medical Sciences Hepatocellular carcinoma HN1 c‐Met prognosis |
| title | Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met |
| title_full | Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met |
| title_fullStr | Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met |
| title_full_unstemmed | Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met |
| title_short | Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met |
| title_sort | increased expression of hematological and neurological expressed 1 hn1 is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down regulation of c met |
| topic | Hepatocellular carcinoma HN1 c‐Met prognosis |
| url | https://doi.org/10.1002/kjm2.12156 |
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