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

Gaza A, Fritz V, Malek L, Wormser L, Treiber N, Danner J, Kremer AE, Thasler WE, Siebler J, Meister G, Neurath MF, Hellerbrand C, Boßerhoff AK, Dietrich P (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Neoplasia Neoplasia

Book Volume: 23

Pages Range: 502-514

Journal Issue: 5

DOI: 10.1016/j.neo.2021.04.001

Abstract

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.

Authors with CRIS profile

Anne Gaza Medizinische Fakultät Valerie Fritz Lehrstuhl für Biochemie und Molekulare Medizin Laura Wormser Lehrstuhl für Biochemie und Molekulare Medizin Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Peter Dietrich Lehrstuhl für Biochemie und Molekulare Medizin

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

D032: The role of neuropeptide Y in chemo-resistance and immune checkpoint inhibition in hepatocellular carcinoma March 1, 2020 - Feb. 28, 2023

Involved external institutions

Universität Regensburg DE Germany (DE) Rotkreuzklinikum München DE Germany (DE)

How to cite

APA:

Gaza, A., Fritz, V., Malek, L., Wormser, L., Treiber, N., Danner, J.,... Dietrich, P. (2021). 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, 23(5), 502-514. https://doi.org/10.1016/j.neo.2021.04.001

MLA:

Gaza, Anne, et al. "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 23.5 (2021): 502-514.

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