ZHX1 Promotes the Proliferation, Migration and Invasion of Cholangiocarcinoma Cells

Kwon, Ryuk-Jun; Han, Myoung‐Eun; Kim, Jiyoung; Liu, Liangwen; Kim, Yun Hak; Jung, Jin-Sup; Oh, Sae‐Ock

doi:10.1371/journal.pone.0165516

Cited by 13 publications

(14 citation statements)

References 32 publications

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“…ZHX1, the first identified factor of this family, has been proposed as a tumor suppressor in many cancer types 29–33. However, two recent studies suggested that ZHX1 may serve as an oncogene in glioblastoma and cholangiocarci- noma 34,35. Upregulated ZHX1 expression in tumor specimens compared with that in normal tissues has been found to be correlated with reduced survival of cancer patients 34,35.…”

Section: Discussionmentioning

confidence: 99%

<p>Attenuated ZHX3 expression serves as a potential biomarker that predicts poor clinical outcomes in breast cancer patients</p>

You

Wang

et al. 2019

CMAR

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BackgroundThe ZHX family has recently been in the spotlight as an integrator and an indispensable node in carcinogenesis, whose expression is frequently dysregulated in multiple cancers. The current study provides a novel investigation of the expression profiles of ZHX factors in breast cancer.Materials and methodsThe mRNA levels of ZHXs and follow-up periods in breast cancer patients were mined through the Oncomine, Cancer Cell Line Encyclopedia, bc-GenExMiner, cBioPortal and Kaplan–Meier plotter databases. In addition, ZHX3 protein expression was examined in 98 primary tumor samples by immunohistochemistry to investigate its association with clinicopathological parameters and patient outcomes.ResultsWe found that the transcriptional levels of ZHX1, ZHX2 and ZHX3 were not significantly altered in tumor tissues compared with those in nontumor tissues. ZHX2 and ZHX3 mRNA levels were observed to be positively correlated with estrogen receptor and progesterone receptor expression, while ZHX2 mRNA levels were negatively associated with HER2 expression. Survival analyses revealed that high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer. Immunohistochemical analysis revealed that patients with decreased ZHX3 protein levels had poorer outcomes. Multivariate analysis exhibited that ZHX3 expression may serve as an independent high-risk prognostic predictor.ConclusionDysregulated expression of ZHXs may be involved in the progression of breast cancer and could serve as a novel biomarker and potential target for breast cancer.

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Section: Discussionmentioning

confidence: 99%

<p>Attenuated ZHX3 expression serves as a potential biomarker that predicts poor clinical outcomes in breast cancer patients</p>

You

Wang

et al. 2019

CMAR

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“…For the Zinc fingers C2H2-type|PR/SET domain family, one of its members, ZHX1 , was regulated by a cluster of five enhancers in 22 samples, which covered 12% of 184 tumor sample with detected super-enhancer regulation. As a transcription repressor, ZHX1 has been associated with the progressions of cholangiocarcinoma, hepatocellular carcinoma, gastric cancer, and breast cancer [ 18 ]. For Pleckstrin homology domain containing genes, there are two AKT proteins ( AKT1/2 ), which regulate cell proliferation and growth.…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer

Liu

Zhao

2017

Oncotarget

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Enhancers are short regulatory regions (50-1500 bp) of DNA that control the tissue-specific activation of gene expression by long distance interaction with targeting gene regions. Recently, genome-wide identification of enhancers in diverse tissues and cell lines was achieved using high-throughput sequencing. Enhancers have been associated with malfunctions in cancer development resulting from point mutations in regulatory regions. However, the potential impact of copy number variations (CNVs) on enhancer regions is unknown. To learn more about the relationship between enhancers and cancer, we integrated the CNVs data on enhancers and explored their targeting gene expression pattern in high-grade ovarian cancer. Using human enhancer-gene interaction data with 13,691 interaction pairs between 7,905 enhancers and 5,297 targeting genes, we found that the 2,910 copy number gain events of enhancer are significantly correlated with the up-regulation of targeting genes. We further identified that a number of highly mutated super-enhancers, with concordant gene expression change on their targeting genes. We also identified 18 targeting genes by super-enhancers with prognostic significance for ovarian cancer, such as the tumour suppressor CDKN1B. We are the first to report that abundant copy number variations on enhancers could change the expression of their targeting genes which would be valuable for the design of enhancer-based cancer treatment strategy.

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“…39 However, in cholangiocarcinoma, hepatocellular carcinoma and cervical cancer, ZHX1 promotes cancer progression. [40][41][42] In glioma, ZHX1…”

Section: Discussionmentioning

confidence: 99%

“…In gastric cancer, ZHX1 impedes the proliferation and migration of cancer cells by inducing cell cycle arrest and apoptosis 39 . However, in cholangiocarcinoma, hepatocellular carcinoma and cervical cancer, ZHX1 promotes cancer progression 40–42 . In glioma, ZHX1 is also shown to be an oncogene, and its high expression can facilitate TWIST1 and SNAI2 expression, comprising crucial modulators in epithelial–mesenchymal transition 22 .…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA SNHG17 promotes proliferation, migration and invasion of glioma cells by regulating the miR‐23b‐3p/ZHX1 axis

2020

The Journal of Gene Medicine

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Background: Long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) is a carcinogenic lncRNA in diverse cancers. The expression pattern and mechanisms of SNHG17 in glioma still await verification. Methods: Paired glioma samples were enrolled. SNHG17, miR-23b-3p, and zincfingers and homeoboxes 1 (ZHX1) mRNA expression were examined by a quantitative real-time polymerase chain reaction (qRT-PCR). SNHG17 short hairpin RNA (shRNA) and miR-23b-3p mimics were transfected into LN229 and U251 cell lines to repress SNHG17 and up-regulate miR-23b-3p expression, respectively. Proliferation, migration and invasion of LN229 and U251 cells were probed by a cell counting kit-8 assay and a Transwell assay. Bioinformatics prediction, dual-luciferase reporter assay, RNA immunoprecipitation assay, qRT-PCR and western blotting were applied to determine the regulatory relationships among SNHG17, miR-23b-3p and ZHX1. Results: SNHG17 expression was markedly raised in glioma tissues, which was positively correlated with ZHX1 expression and negatively associated with the expression of miR-23b-3p. After transfection of SNHG17 shRNAs into glioma cells, the proliferation, migration and invasion of cancer cells was markedly restrained. miR-23b-3p mimics the function of SHNG17 knockdown. Furthermore, miR-23b-3p was shown to be negatively modulated by SNHG17, and ZHX1 was identified as a target of miR-23b-3p. Conclusions: SNHG17 is a "competing endogenous RNA" with respect to modulating ZHX1 expression by adsorbing miR-23b-3p and thereby promoting glioma progression.

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ZHX1 Promotes the Proliferation, Migration and Invasion of Cholangiocarcinoma Cells

Cited by 13 publications

References 32 publications

<p>Attenuated ZHX3 expression serves as a potential biomarker that predicts poor clinical outcomes in breast cancer patients</p>

<p>Attenuated ZHX3 expression serves as a potential biomarker that predicts poor clinical outcomes in breast cancer patients</p>

Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer

Long non‐coding RNA SNHG17 promotes proliferation, migration and invasion of glioma cells by regulating the miR‐23b‐3p/ZHX1 axis

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