Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11
The poor prognosis of advanced hepatocellular carcinoma (HCC) is driven by diverse features including dysregulated microRNAs inducing drug resistance and stemness. Lin-28 homolog A (LIN28A) and its partner zinc finger CCHC-type containing 11 (ZCCHC11) cooperate in binding, oligouridylation and subse...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655862100021X |
| _version_ | 1830307012734353408 |
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| author | Anne Gaza Valerie Fritz Lara Malek Laura Wormser Nora Treiber Johannes Danner Andreas E. Kremer Wolfgang E. Thasler Jürgen Siebler Gunter Meister Markus F. Neurath Claus Hellerbrand Anja K. Bosserhoff Peter Dietrich |
| author_facet | Anne Gaza Valerie Fritz Lara Malek Laura Wormser Nora Treiber Johannes Danner Andreas E. Kremer Wolfgang E. Thasler Jürgen Siebler Gunter Meister Markus F. Neurath Claus Hellerbrand Anja K. Bosserhoff Peter Dietrich |
| author_sort | Anne Gaza |
| collection | DOAJ |
| description | The poor prognosis of advanced hepatocellular carcinoma (HCC) is driven by diverse features including dysregulated microRNAs inducing drug resistance and stemness. Lin-28 homolog A (LIN28A) and its partner zinc finger CCHC-type containing 11 (ZCCHC11) cooperate in binding, oligouridylation and subsequent degradation of tumorsuppressive let-7 precursor microRNAs. Functionally, activation of LIN28A was recently shown to promote stemness and chemoresistance in HCC. However, the expression and regulation of LIN28A in HCC had been unclear. Moreover, the expression, regulation and function of ZCCHC11 in liver cancer remained elusive.In contrast to ''one-microRNA-one-target'' interactions, we identified common binding sites for miR-622 in both LIN28A and ZCCHC11, suggesting miR-622 to function as a superior pathway regulator. Applying comprehensive microRNA database screening, human hepatocytes and HCC cell lines, patient-derived tissue samples as well as ''The Cancer Genome Atlas'' (TCGA) patient cohorts, we demonstrated that loss of tumorsuppressive miR-622 mediates derepression and overexpression of LIN28A in HCC. Moreover, the cooperator of LIN28A, ZCCHC11, was newly identified as a prognostic and therapeutic target of miR-622 in liver cancer.Together, identification of novel miR-622 target genes revealed common regulation of cooperating genes and outlines the previously unknown oncogenic role of ZCCHC11 in liver cancer. |
| first_indexed | 2024-12-19T10:24:03Z |
| format | Article |
| id | doaj.art-ce90753935094bce83d17dd21852b8b8 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-19T10:24:03Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-ce90753935094bce83d17dd21852b8b82022-12-21T20:25:57ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862021-05-01235502514Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11Anne Gaza0Valerie Fritz1Lara Malek2Laura Wormser3Nora Treiber4Johannes Danner5Andreas E. Kremer6Wolfgang E. Thasler7Jürgen Siebler8Gunter Meister9Markus F. Neurath10Claus Hellerbrand11Anja K. Bosserhoff12Peter Dietrich13Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyBiochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, GermanyBiochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, GermanyDepartment of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, GermanyDepartment of General and Visceral Surgery, Red Cross Hospital of Munich, GermanyDepartment of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, GermanyBiochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, GermanyDepartment of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany; Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany; Corresponding author.The poor prognosis of advanced hepatocellular carcinoma (HCC) is driven by diverse features including dysregulated microRNAs inducing drug resistance and stemness. Lin-28 homolog A (LIN28A) and its partner zinc finger CCHC-type containing 11 (ZCCHC11) cooperate in binding, oligouridylation and subsequent degradation of tumorsuppressive let-7 precursor microRNAs. Functionally, activation of LIN28A was recently shown to promote stemness and chemoresistance in HCC. However, the expression and regulation of LIN28A in HCC had been unclear. Moreover, the expression, regulation and function of ZCCHC11 in liver cancer remained elusive.In contrast to ''one-microRNA-one-target'' interactions, we identified common binding sites for miR-622 in both LIN28A and ZCCHC11, suggesting miR-622 to function as a superior pathway regulator. Applying comprehensive microRNA database screening, human hepatocytes and HCC cell lines, patient-derived tissue samples as well as ''The Cancer Genome Atlas'' (TCGA) patient cohorts, we demonstrated that loss of tumorsuppressive miR-622 mediates derepression and overexpression of LIN28A in HCC. Moreover, the cooperator of LIN28A, ZCCHC11, was newly identified as a prognostic and therapeutic target of miR-622 in liver cancer.Together, identification of novel miR-622 target genes revealed common regulation of cooperating genes and outlines the previously unknown oncogenic role of ZCCHC11 in liver cancer.http://www.sciencedirect.com/science/article/pii/S147655862100021XHepatocellular carcinomaHCCmicroRNAdrug resistanceZCCHC11 |
| spellingShingle | Anne Gaza Valerie Fritz Lara Malek Laura Wormser Nora Treiber Johannes Danner Andreas E. Kremer Wolfgang E. Thasler Jürgen Siebler Gunter Meister Markus F. Neurath Claus Hellerbrand Anja K. Bosserhoff Peter Dietrich Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11 Neoplasia: An International Journal for Oncology Research Hepatocellular carcinoma HCC microRNA drug resistance ZCCHC11 |
| title | Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11 |
| title_full | Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11 |
| title_fullStr | Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11 |
| title_full_unstemmed | Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11 |
| title_short | Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11 |
| title_sort | identification of novel targets of mir 622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger cchc type containing 11 |
| topic | Hepatocellular carcinoma HCC microRNA drug resistance ZCCHC11 |
| url | http://www.sciencedirect.com/science/article/pii/S147655862100021X |
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