PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma
Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger pro...
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Veröffentlicht in: | Experimental cell research 2021-09, Vol.406 (1), p.112690-112690, Article 112690 |
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creator | Xiaoyun, Shi Yuyuan, Zi Jie, Xing Yingjie, Nie Qing, Xie Yuezhen, Deng Haiguang, Xin |
description | Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. In a biological function study, PHF19 was found to promote the growth of HCC cells both in liquid culture and in soft agar. Moreover, knocking out PHF19 in a HCC mouse model (MycF/F) using the hydrodynamic method inhibited tumorigenesis and improved survival. Taken together, these results demonstrate that PHF19 promotes the growth of HCC cells by activating the Hedgehog signaling pathway. |
doi_str_mv | 10.1016/j.yexcr.2021.112690 |
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However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. In a biological function study, PHF19 was found to promote the growth of HCC cells both in liquid culture and in soft agar. Moreover, knocking out PHF19 in a HCC mouse model (MycF/F) using the hydrodynamic method inhibited tumorigenesis and improved survival. 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However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. In a biological function study, PHF19 was found to promote the growth of HCC cells both in liquid culture and in soft agar. Moreover, knocking out PHF19 in a HCC mouse model (MycF/F) using the hydrodynamic method inhibited tumorigenesis and improved survival. Taken together, these results demonstrate that PHF19 promotes the growth of HCC cells by activating the Hedgehog signaling pathway.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>AGAR</subject><subject>BIOLOGICAL FUNCTIONS</subject><subject>Cell growth</subject><subject>Hedgehog-Gli1 signaling pathway</subject><subject>Hepatocellular carcinoma</subject><subject>HEPATOMAS</subject><subject>HYDRODYNAMICS</subject><subject>LIGASES</subject><subject>MICE</subject><subject>PHF19</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE9v1DAUxK0KpC6ln6CXSFy4ZOt_cZwDB1RRilSpHODAyXqyn7NeJfZieyv67ZsQzpze4c1vNDOE3DC6Z5Sp2-P-Bf_YvOeUsz1jXA30guwYHWjLJedvyI5SJlupeX9J3pVypJRqzdSO_Pr-cM-GBmwNz1CxNAd0Ix7S2JQwRphCHBuIrjnlNKf1X89zymHEiCWUJsQFOEFNFqfpPEFuLGQbYprhPXnrYSp4_e9ekZ_3X37cPbSPT1-_3X1-bK1QsrbS9-hBKdFrpSVyir1A5xgI710HSAfQgNZRzcBSr6Vn3inWa6E6JbUTV-TD5ptKDabYUNEebIoRbTVcsKHrJF9UHzfVUuT3GUs1cyhraIiYzsXwTi6eindikYpNanMqJaM3pxxmyC-GUbPObY7m79xmndtscy_Up43CpetzwLxGwWjRhbwmcSn8l38FqceKnw</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Xiaoyun, Shi</creator><creator>Yuyuan, Zi</creator><creator>Jie, Xing</creator><creator>Yingjie, Nie</creator><creator>Qing, Xie</creator><creator>Yuezhen, Deng</creator><creator>Haiguang, Xin</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20210901</creationdate><title>PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma</title><author>Xiaoyun, Shi ; Yuyuan, Zi ; Jie, Xing ; Yingjie, Nie ; Qing, Xie ; Yuezhen, Deng ; Haiguang, Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-4f7efa66378684e20e73edd1a3ffd5ae09a8aecd081ac0f84f1fd6178365648d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>AGAR</topic><topic>BIOLOGICAL FUNCTIONS</topic><topic>Cell growth</topic><topic>Hedgehog-Gli1 signaling pathway</topic><topic>Hepatocellular carcinoma</topic><topic>HEPATOMAS</topic><topic>HYDRODYNAMICS</topic><topic>LIGASES</topic><topic>MICE</topic><topic>PHF19</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiaoyun, Shi</creatorcontrib><creatorcontrib>Yuyuan, Zi</creatorcontrib><creatorcontrib>Jie, Xing</creatorcontrib><creatorcontrib>Yingjie, Nie</creatorcontrib><creatorcontrib>Qing, Xie</creatorcontrib><creatorcontrib>Yuezhen, Deng</creatorcontrib><creatorcontrib>Haiguang, Xin</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiaoyun, Shi</au><au>Yuyuan, Zi</au><au>Jie, Xing</au><au>Yingjie, Nie</au><au>Qing, Xie</au><au>Yuezhen, Deng</au><au>Haiguang, Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma</atitle><jtitle>Experimental cell research</jtitle><date>2021-09-01</date><risdate>2021</risdate><volume>406</volume><issue>1</issue><spage>112690</spage><epage>112690</epage><pages>112690-112690</pages><artnum>112690</artnum><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. 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subjects | 60 APPLIED LIFE SCIENCES AGAR BIOLOGICAL FUNCTIONS Cell growth Hedgehog-Gli1 signaling pathway Hepatocellular carcinoma HEPATOMAS HYDRODYNAMICS LIGASES MICE PHF19 |
title | PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma |
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