DSN1 Interaction With Centromere‐Associated Proteins Promotes Chromosomal Instability in Hepatocellular Carcinoma
ABSTRACT Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Dosage suppressor of NNF1 (DSN1), a component of the MIS12 kinetochore complex, encodes a kinetochore protein crucial for proper mitotic assembly. The role of DSN1 in HCC remains to be elucidated. In this study, we u...
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| Veröffentlicht in: | Molecular carcinogenesis 2025-02, Vol.64 (2), p.329-343 |
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| creator | Zhou, Hongrui Zhang, Mengxue Lian, Jiabing Wang, Ruichang Yang, Zhe Wang, Jin Bi, Xiuli |
| description | ABSTRACT
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Dosage suppressor of NNF1 (DSN1), a component of the MIS12 kinetochore complex, encodes a kinetochore protein crucial for proper mitotic assembly. The role of DSN1 in HCC remains to be elucidated. In this study, we utilized The Cancer Genome Atlas, the Hepatocellular carcinoma Cell Database, and other databases to analyze DSN1 expression and prognosis in samples from patients with HCC. We investigated the signaling pathways regulated by DSN1 and their implications in HCC. Additionally, we engineered siRNA/shRNA and overexpression vectors for DSN1 and assessed the specific mechanisms of regulatory pathways of DSN1 in hepatoma cell lines and subcutaneous tumor xenograft model. Our findings revealed that DSN1 expression was significantly upregulated in patients with HCC, correlating with decreased survival rates. Elevated DSN1 expression led to the overproduction of cell cycle‐related proteins through direct interaction with Centromere Protein T. This interaction contributes to chromosomal instability in patients with HCC, resulting in an aberrant cell cycle and fostering the development and progression of HCC. Increased DSN1 expression is pivotal in HCC initiation and progression. Investigating DSN1 offers valuable insights into the pathogenesis, treatment, and prevention of HCC. |
| doi_str_mv | 10.1002/mc.23845 |
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Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Dosage suppressor of NNF1 (DSN1), a component of the MIS12 kinetochore complex, encodes a kinetochore protein crucial for proper mitotic assembly. The role of DSN1 in HCC remains to be elucidated. In this study, we utilized The Cancer Genome Atlas, the Hepatocellular carcinoma Cell Database, and other databases to analyze DSN1 expression and prognosis in samples from patients with HCC. We investigated the signaling pathways regulated by DSN1 and their implications in HCC. Additionally, we engineered siRNA/shRNA and overexpression vectors for DSN1 and assessed the specific mechanisms of regulatory pathways of DSN1 in hepatoma cell lines and subcutaneous tumor xenograft model. Our findings revealed that DSN1 expression was significantly upregulated in patients with HCC, correlating with decreased survival rates. Elevated DSN1 expression led to the overproduction of cell cycle‐related proteins through direct interaction with Centromere Protein T. This interaction contributes to chromosomal instability in patients with HCC, resulting in an aberrant cell cycle and fostering the development and progression of HCC. Increased DSN1 expression is pivotal in HCC initiation and progression. Investigating DSN1 offers valuable insights into the pathogenesis, treatment, and prevention of HCC.</description><identifier>ISSN: 0899-1987</identifier><identifier>ISSN: 1098-2744</identifier><identifier>EISSN: 1098-2744</identifier><identifier>DOI: 10.1002/mc.23845</identifier><identifier>PMID: 39560395</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Cell cycle ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; cell cycle regulation ; Cell Line, Tumor ; Cell Proliferation - genetics ; Cell survival ; Chromosomal Instability ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - metabolism ; DSN1 ; Expression vectors ; Female ; Gene Expression Regulation, Neoplastic ; Genomic instability ; Hepatocellular carcinoma ; Hepatoma ; Humans ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Male ; Medical prognosis ; Mice ; Mice, Nude ; Prognosis ; siRNA ; Tumor cell lines ; Xenograft Model Antitumor Assays</subject><ispartof>Molecular carcinogenesis, 2025-02, Vol.64 (2), p.329-343</ispartof><rights>2024 Wiley Periodicals LLC.</rights><rights>2025 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2405-2e59e46b6c789999a85c6697b11b503dacf46fad7d3da82cd6aa229942b5fb6d3</cites><orcidid>0000-0002-9065-1151</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmc.23845$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmc.23845$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39560395$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Hongrui</creatorcontrib><creatorcontrib>Zhang, Mengxue</creatorcontrib><creatorcontrib>Lian, Jiabing</creatorcontrib><creatorcontrib>Wang, Ruichang</creatorcontrib><creatorcontrib>Yang, Zhe</creatorcontrib><creatorcontrib>Wang, Jin</creatorcontrib><creatorcontrib>Bi, Xiuli</creatorcontrib><title>DSN1 Interaction With Centromere‐Associated Proteins Promotes Chromosomal Instability in Hepatocellular Carcinoma</title><title>Molecular carcinogenesis</title><addtitle>Mol Carcinog</addtitle><description>ABSTRACT
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Dosage suppressor of NNF1 (DSN1), a component of the MIS12 kinetochore complex, encodes a kinetochore protein crucial for proper mitotic assembly. The role of DSN1 in HCC remains to be elucidated. In this study, we utilized The Cancer Genome Atlas, the Hepatocellular carcinoma Cell Database, and other databases to analyze DSN1 expression and prognosis in samples from patients with HCC. We investigated the signaling pathways regulated by DSN1 and their implications in HCC. Additionally, we engineered siRNA/shRNA and overexpression vectors for DSN1 and assessed the specific mechanisms of regulatory pathways of DSN1 in hepatoma cell lines and subcutaneous tumor xenograft model. Our findings revealed that DSN1 expression was significantly upregulated in patients with HCC, correlating with decreased survival rates. Elevated DSN1 expression led to the overproduction of cell cycle‐related proteins through direct interaction with Centromere Protein T. This interaction contributes to chromosomal instability in patients with HCC, resulting in an aberrant cell cycle and fostering the development and progression of HCC. Increased DSN1 expression is pivotal in HCC initiation and progression. Investigating DSN1 offers valuable insights into the pathogenesis, treatment, and prevention of HCC.</description><subject>Animals</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>cell cycle regulation</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - genetics</subject><subject>Cell survival</subject><subject>Chromosomal Instability</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>DSN1</subject><subject>Expression vectors</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genomic instability</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatoma</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Prognosis</subject><subject>siRNA</subject><subject>Tumor cell lines</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0899-1987</issn><issn>1098-2744</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd1KwzAYhoMobk7BK5CCJ550JmmTNoej_mwwf0DFw5KmKctom5mkyM68BK_RKzF1U0Hw5Pveg4eH7weAYwTHCEJ83ogxjtKY7IAhgiwNcRLHu2AIU8ZCxNJkAA6sXUKIUELgPhhEjFDoyxDYi4dbFMxaJw0XTuk2eFZuEWSydUY30siPt_eJtVoo7mQZ3BvtpGptHxofbZAt-mR1w2uvsY4XqlZuHag2mMoVd1rIuu5qboKMG6FaDx6CvYrXVh5t-wg8XV0-ZtNwfnc9yybzUOAYkhBLwmRMCyoSvwdjPCWCUpYUCBUERiUXVUwrXialzykWJeUcY8ZiXJCqoGU0Amcb78rol05alzfK9uPwVurO5hGKIEaIYOTR0z_oUnem9dN5ihAcYZqwX6Ew2lojq3xlVMPNOkcw7x-RNyL_eoRHT7bCrmhk-QN-X94D4QZ4VbVc_yvKb7KN8BP9s5Lu</recordid><startdate>202502</startdate><enddate>202502</enddate><creator>Zhou, Hongrui</creator><creator>Zhang, Mengxue</creator><creator>Lian, Jiabing</creator><creator>Wang, Ruichang</creator><creator>Yang, Zhe</creator><creator>Wang, Jin</creator><creator>Bi, Xiuli</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9065-1151</orcidid></search><sort><creationdate>202502</creationdate><title>DSN1 Interaction With Centromere‐Associated Proteins Promotes Chromosomal Instability in Hepatocellular Carcinoma</title><author>Zhou, Hongrui ; Zhang, Mengxue ; Lian, Jiabing ; Wang, Ruichang ; Yang, Zhe ; Wang, Jin ; Bi, Xiuli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2405-2e59e46b6c789999a85c6697b11b503dacf46fad7d3da82cd6aa229942b5fb6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Animals</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>cell cycle regulation</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - genetics</topic><topic>Cell survival</topic><topic>Chromosomal Instability</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - metabolism</topic><topic>DSN1</topic><topic>Expression vectors</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genomic instability</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatoma</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Prognosis</topic><topic>siRNA</topic><topic>Tumor cell lines</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Hongrui</creatorcontrib><creatorcontrib>Zhang, Mengxue</creatorcontrib><creatorcontrib>Lian, Jiabing</creatorcontrib><creatorcontrib>Wang, Ruichang</creatorcontrib><creatorcontrib>Yang, Zhe</creatorcontrib><creatorcontrib>Wang, Jin</creatorcontrib><creatorcontrib>Bi, Xiuli</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular carcinogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Hongrui</au><au>Zhang, Mengxue</au><au>Lian, Jiabing</au><au>Wang, Ruichang</au><au>Yang, Zhe</au><au>Wang, Jin</au><au>Bi, Xiuli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DSN1 Interaction With Centromere‐Associated Proteins Promotes Chromosomal Instability in Hepatocellular Carcinoma</atitle><jtitle>Molecular carcinogenesis</jtitle><addtitle>Mol Carcinog</addtitle><date>2025-02</date><risdate>2025</risdate><volume>64</volume><issue>2</issue><spage>329</spage><epage>343</epage><pages>329-343</pages><issn>0899-1987</issn><issn>1098-2744</issn><eissn>1098-2744</eissn><abstract>ABSTRACT
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Dosage suppressor of NNF1 (DSN1), a component of the MIS12 kinetochore complex, encodes a kinetochore protein crucial for proper mitotic assembly. The role of DSN1 in HCC remains to be elucidated. In this study, we utilized The Cancer Genome Atlas, the Hepatocellular carcinoma Cell Database, and other databases to analyze DSN1 expression and prognosis in samples from patients with HCC. We investigated the signaling pathways regulated by DSN1 and their implications in HCC. Additionally, we engineered siRNA/shRNA and overexpression vectors for DSN1 and assessed the specific mechanisms of regulatory pathways of DSN1 in hepatoma cell lines and subcutaneous tumor xenograft model. Our findings revealed that DSN1 expression was significantly upregulated in patients with HCC, correlating with decreased survival rates. Elevated DSN1 expression led to the overproduction of cell cycle‐related proteins through direct interaction with Centromere Protein T. This interaction contributes to chromosomal instability in patients with HCC, resulting in an aberrant cell cycle and fostering the development and progression of HCC. Increased DSN1 expression is pivotal in HCC initiation and progression. Investigating DSN1 offers valuable insights into the pathogenesis, treatment, and prevention of HCC.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39560395</pmid><doi>10.1002/mc.23845</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-9065-1151</orcidid></addata></record> |
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| subjects | Animals Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Cell cycle Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism cell cycle regulation Cell Line, Tumor Cell Proliferation - genetics Cell survival Chromosomal Instability Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - metabolism DSN1 Expression vectors Female Gene Expression Regulation, Neoplastic Genomic instability Hepatocellular carcinoma Hepatoma Humans Liver cancer Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Male Medical prognosis Mice Mice, Nude Prognosis siRNA Tumor cell lines Xenograft Model Antitumor Assays |
| title | DSN1 Interaction With Centromere‐Associated Proteins Promotes Chromosomal Instability in Hepatocellular Carcinoma |
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