HN1L-mediated transcriptional axis AP-2γ/METTL13/TCF3-ZEB1 drives tumor growth and metastasis in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies and lacks targeted therapies. Here, we reported a novel potential therapeutic target hematological and neurological expressed 1 like ( HN1L ) in HCC. First, HCC tissue microarray analysis showed that HN1L was frequently up-reg...
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Veröffentlicht in: | Cell death and differentiation 2019-11, Vol.26 (11), p.2268-2283 |
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Sprache: | eng |
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Zusammenfassung: | Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies and lacks targeted therapies. Here, we reported a novel potential therapeutic target hematological and neurological expressed 1 like (
HN1L
) in HCC. First, HCC tissue microarray analysis showed that HN1L was frequently up-regulated in cancer tissues than that in normal liver tissues, which significantly associated with tumor size, local invasion, distant metastases, and poor prognosis for HCC patients. Functional studies demonstrated that ectopic expression of
HN1L
could increase cell growth, foci formation in monolayer culture, colony formation in soft agar and tumorigenesis in nude mice. In addition, HN1L could also promote HCC metastasis by inducing epithelial-mesenchymal transition. Inversely, silencing
HN1L
expression with shRNA could effectively attenuate its oncogenic function. We further showed that HN1L transcriptionally up-regulated methyltransferase like 13 (
METTL13
) gene in an AP-2γ dependent manner, which promoted cell proliferation and metastasis by up-regulating
TCF3
and
ZEB1
. Importantly, administration of lentivirus-mediated shRNA interfering
HN1L
expression could inhibit tumorigenesis and metastasis in mice. Collectively,
HN1L
-mediated transcriptional axis AP-2γ/METTL13/TCF3-ZEB1 promotes HCC growth and metastasis representing a promising therapeutic target in HCC treatment. |
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ISSN: | 1350-9047 1476-5403 |
DOI: | 10.1038/s41418-019-0301-1 |