Roles of zinc-fingers and homeoboxes 1 during the proliferation, migration, and invasion of glioblastoma cells

Abstract

Zinc-fingers and homeoboxes 1 (ZHX1) is a nuclear transcription repressor and known to be involved in cell differentiation and tumorigenesis. However, the pathophysiological roles of ZHX1 have not been characterized in glioblastoma. We examined ZHX1 expression in glioblastoma patients' tissues and analyzed overall survival of the patients based on expression level of ZHX1. We also examined the effects of ZHX1 on proliferation and motility of glioblastoma cells. In silico analysis and immunohistochemical studies showed that the messenger RNA and protein expressions of ZHX1 were higher in the tissues of glioblastoma patients than in normal brain tissues, and that its overexpression was associated with reduced survival. In vitro, the downregulation of ZHX1 decreased the proliferation, migration, and invasion of glioblastoma cells, whereas its upregulation had the opposite effects. In addition, we showed ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2. Taken together, this study demonstrates that ZHX1 plays crucial roles in the progression of glioblastoma, and its findings suggest that ZHX1 be viewed as a potential prognostic maker and therapeutic target of glioblastoma.

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

“…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. The observations in glioblastoma and cholangiocarcinoma are consistent with our findings, ie, patients with high ZHX1 expression showed significantly prolonged OS than those with low ZHX1 expression.…”

“…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.…”

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

“…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 It is worth noting that elevated ZHX1 expression is correlated with a poor prognosis in GBM patients, and an in vitro study suggested that ZHX1 inhibits GBM cell apoptosis via Bax down-regulation and Bcl-2 up-regulation. 43 In the present study, we showed that miR-23b-3p could negatively modulate ZHX1 expression; in addition, SNHG17 knockdown could reduce ZHX1 expression, thus clarifying the downstream mechanism of SNHG17/ miR-23b-3p and explaining the dysregulation of ZHX1 in glioma.…”

“…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 . It is worth noting that elevated ZHX1 expression is correlated with a poor prognosis in GBM patients, and an in vitro study suggested that ZHX1 inhibits GBM cell apoptosis via Bax down‐regulation and Bcl‐2 up‐regulation 43 .…”

“…Zinc‐fingers and homeoboxes 1 (ZHX1), affiliated to the ZHX protein family, can be localized in the nucleus to regulate transcription 20,21 . It has been demonstrated that ZHX1 expression in glioblastoma tissue is higher than that in normal brain tissue, and its overexpression is associated with a decreased survival rate; ZHX1 positively modulates the proliferation, migration and invasion of glioblastoma cells, 22 implying that ZHX1 is involved in the progression of glioma, although its upstream mechanism needs to be explored further.…”