Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

Abstract

Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC.

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

“…However, another report revealed that ZHX2 protein expression was observed only in cancer tissues and associated with advanced clinical stage and metastasis of hepatocellular carcinoma 43. Another recent study showed downregulated ZHX3 expression and upregulated ZHX2 expression in renal cell carcinoma, and the expression levels of ZHX1 and ZHX3 were significantly associated with pathological stage 32. Decreased ZHX2 expression has also been found to be correlated with an unfavorable outcome in multiple myeloma 44.…”

HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation

“…Decreased expression of ZHX2 in Hodgkin lymphoma is associated with a translocation between chromosomes 4q27 and 8q24, the location of ZHX2. 47 Of particular interest are the mechanisms by which ZHX2 expression is inhibited in HCC. 46 In contrast, ZHX2 appears to be higher expressed in renal cell carcinoma.…”

“…46 In contrast, ZHX2 appears to be higher expressed in renal cell carcinoma. 47 Of particular interest are the mechanisms by which ZHX2 expression is inhibited in HCC. One study observed ZHX2 promoter hypermethylation and reduced ZHX2 levels in HCC, 20 indicating epigenetic regulation of ZHX2.…”

Host Transcription Factors in Hepatitis B Virus RNA Synthesis

“…Zinc finger and homeoboxes 2 (ZHX2) is also a liver-enriched transcriptional repressor in adult hepatocytes and a tumor suppressor [265,266]. It is important for hepatocyte gene regulation and liver development and plays roles in renal cancer and stem cell differentiation [267][268][269][270]. ZHX2 contains four homeodomains and two C2H2 zinc finger motifs that allow for DNA binding causing transcriptional repression as both a homodimer ( Figure 3F) or a heterodimer when bound with ZHX1 [265,271].…”