Zinc finger protein 185 is a liver metastasis-associated factor in colon cancer patients

Furukawa, Daisuke; Chijiwa, Tsuyoshi; Matsuyama, Masahiro; Mukai, Masaya; Matsuo, Ei‐ichi; Nishimura, Osamu; Kawai, Kenji; Suemizu, Hiroshi; Hiraoka, Nobuyoshi; Nakagohri, Toshio; Yasuda, Seiei; Nakamura, Masato

doi:10.3892/mco.2014.298

Cited by 15 publications

(16 citation statements)

References 33 publications

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“…ZNF185, also known as ZFP185, is belonging to the ZNF family and identified by Heiss for the first time in 1997 (16). ZNF185 is located on DXS52 region of the long arm of chromosome Xq28 (16), with a LIM zinc-binding domain at the C terminus and an actin-targeting domain at the N terminus (17). The previous study indicates that ZNF185 is involved in cell proliferation and cell differentiation (18,19).…”

Section: Introductionmentioning

confidence: 99%

Expression pattern of Zinc finger protein 185 in mouse testis and its role in regulation of testosterone secretion

You

Fan

et al. 2017

Molecular Medicine Reports

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Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in cell proliferation and differentiation. To the best of our knowledge, the association between ZNF185 and male reproduction is unknown. In the present study, the expression and localization of ZNF185 in mouse testis, as well as its role in testosterone secretion, cell cycle progression and apoptosis of mouse Leydig cells were investigated. The results of the immunofluorescence analysis indicated that ZNF185 was highly expressed in Leydig cells of the mouse testis, and primarily localized in the cytoplasm. The results of quantitative polymerase chain reaction and western blot analyses further validated that ZNF185 expression was significantly higher in Leydig cells and sperm compared with that in Sertoli cells. Subsequently, the expression pattern of ZNF185 in mouse testis was determined at different developmental stages. The results demonstrated that the expression of ZNF185 was highest in the testis of 10‑week‑old mice and lowest in 2‑week‑old mice. Furthermore, the role of ZNF185 in Leydig cells of the mouse testis was investigated. Different concentrations of luteinizing hormone (LH) were used to stimulate the Leydig cells and subsequently the expression of ZNF185, and testosterone concentration was detected. The results revealed that LH upregulated the expression of ZNF185 and testosterone secretion, and ZNF185 expression was significantly positively correlated with testosterone secretion. To further validate whether ZNF185 was involved in testosterone secretion, lentiviral‑mediated RNA interference was used to knock down ZNF185 expression in Leydig cells. The results demonstrated that ZNF185 expression and testosterone secretion of Leydig cells were decreased significantly. In addition, the results demonstrated that the knockdown of ZNF185 expression did not significantly affect cell cycle progression or apoptosis. Taken together, the results of the present study revealed that ZNF185 was highly expressed in Leydig cells of the testis and involved in the secretion of testosterone. These results have contributed to the elucidation of the mechanism underlying male reproduction and may provide a novel target for the treatment of infertility, and the development of a contraceptive vaccine.

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Section: Introductionmentioning

confidence: 99%

Expression pattern of Zinc finger protein 185 in mouse testis and its role in regulation of testosterone secretion

You

Fan

et al. 2017

Molecular Medicine Reports

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“…Sections (4-µm-thick) of representative formalin-fixed paraffin-embedded tissue blocks stained with a rabbit antibody specific to ZNF185 (Sigma-Aldrich; Merck KGaA) were used, as per the protocol of our previous study ( 12 ). The sections were incubated in 0.3% H 2 O 2 in methanol at room temperature for 30 min to block endogenous peroxidase reaction.…”

Section: Methodsmentioning

confidence: 99%

“…In order to understand the mechanisms underlying hematogenous metastasis in PDC, the molecular expression profile of the BxPC-3 PDC cell line, which demonstrates weak metastasis to the liver, was previously compared with that of the highly metastatic LM-BxPC-3 subline ( 11 ). This led to the isolation of ZNF185 as a metastasis-associated protein by global quantitative proteome analysis ( 12 ). ZNF185 contains two zinc-finger motifs in the C-terminus that fit the consensus pattern of a LIM domain ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…At present, the biological and clinical significance of ZNF185 in cancer has not been investigated extensively. Only a small number of studies have focused on ZNF185 in the context of cancer: One group concluded that ZNF185 serves a tumor-suppressive role in prostate cancer ( 14 ), whereas another group considered ZNF185 to be an unfavorable prognostic indicator in colon cancer ( 12 ). In the present study, the clinicopathological significance of ZNF185 in PDC was investigated.…”

Section: Introductionmentioning

confidence: 99%

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Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma

Furukawa¹,

Chijiwa

Matsuyama

et al. 2017

Oncology Letters

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Pancreatic ductal carcinoma (PDC) is one of the major causes of cancer-associated mortality globally due to its high potential for distant metastasis. To understand hematogenous metastasis, the molecular expression profiles of weak metastatic PDC cell subline BxPC-3 and highly liver-metastatic cell subline LM-BxPC-3 were compared, and zinc finger protein 185 (ZNF185) was identified as a molecule that is upregulated in LM-BxPC-3 cells. The aim of the present study was to evaluate the clinicopathological significance of ZNF185 in PDC. Using immunohistochemistry, ZNF185 expression was investigated in 182 patients with PDC, in association with numerous clinicopathological variables. The expression profile of ZNF185 was also characterized using xenograft models. In contrast to parent BxPC-3 cells in subcutaneous transplanted tumor foci, which only expressed ZNF185 on their plasma membrane (m)ZNF185, LM-BxPC-3 cells in liver-metastatic foci that were formed subsequent to transplantation all expressed cytoplasmic (c)ZNF185. Additionally, 51% of the cells at the periphery of the tumor foci expressed mZNF185. Expression of cZNF185, and of mZNF185 and cZNF185 combined was identified in 93 and 39% of clinical patients with PDC, respectively. Patients with mZNF185-negative and -positive PDC exhibited a median survival time of 30.2 months and 21.3 months, respectively. Multivariate analysis indicated that the expression of mZNF185 is closely associated with a shorter overall survival time. Increased marked venous invasion was more prevalent in patients who were mZNF185-positive, as compared with patients who were mZNF185-negative. These data suggest that the expression of mZNF185 is an independent and unfavorable prognosticator in patients with PDC. The results suggested that the amount and subcellular location of ZNF185 are correlated with the position of the cancer cells expressing it within the nests. Additionally, the subcellular location of ZNF185 may be important to its biological function.

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“…It is located on the DXS52 region of chromosome Xq28 . ZNF185 contains an actin‐targeting domain at the N‐terminus and an LIM zinc‐binding domain at the C‐terminus . A previous study by our group showed that expression of ZNF185 in mouse testis was significantly higher than that in other tissues and was highly expressed particularly in the Leydig cells and sperm.…”

Section: Introductionmentioning

confidence: 93%

ZNF185‐derived peptide induces fertility suppression in mice

Fan

Zhao

Pan

et al. 2018

Journal of Peptide Science

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Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in male reproduction. However, it is unclear whether ZNF185 may be a target candidate for contraceptive vaccines. In this study, antigenic peptides derived from ZNF185 were prepared, and their immune contraceptive effects were investigated using mice. Results from enzyme‐linked immunosorbent assay (ELISAs) showed that peptide immunization induced an antibody titre increase that reached a peak in week 12. Peptide‐3 and peptide‐4 were then chosen for subsequent experiments. The results of the fertility assays showed that peptide immunization inhibited the mating and fertility rates of the mice, whereas there were no obvious changes in the number of pups per litter. Subsequently, epididymal sperm was analysed. The results demonstrated that the sperm count and sperm motility were significantly decreased in the peptide group, while the amount of abnormal sperm was significantly increased in the peptide‐3 group. The male reproductive organs were also evaluated. There were no obvious differences in testis or epididymal weights, in the diameters of the seminiferous tubules, or in the thicknesses of the seminiferous epithelium between the peptide group and the phosphate buffer saline (PBS) group. In addition, histological analysis indicated that there were no obvious pathologic changes in testis and epididymal histology in the peptide group; however, the number of spermatozoa present in the epididymal lumen of the peptide group was significantly decreased when compared with the PBS group. Our study demonstrates for the first time that peptides derived from ZNF185 may induce fertility suppression in mice without damaging reproductive organs. These peptides have the potential to be used as a male contraceptive vaccine.

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Zinc finger protein 185 is a liver metastasis-associated factor in colon cancer patients

Cited by 15 publications

References 33 publications

Expression pattern of Zinc finger protein 185 in mouse testis and its role in regulation of testosterone secretion

Expression pattern of Zinc finger protein 185 in mouse testis and its role in regulation of testosterone secretion

Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma

ZNF185‐derived peptide induces fertility suppression in mice

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