NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma

Abstract

NF45, also referred to as nuclear factor of activated T cells, has been reported to promote the progression of multiple cancer types. However, the expression and physiological significance of NF45 in pancreatic ductal adenocarcinoma (PDAC) remain largely elusive. In this study, we investigated the clinical relevance and potential role of NF45 expression in PDAC development. Western blot analysis revealed that NF45 was remarkably upregulated in PDAC tissues, compared with the adjacent non-tumorous ones. In addition, the expression of NF45 in 122 patients with PDAC was evaluated using immunohistochemistry. In this way, we found that NF45 was abundantly expressed in PDAC tissues, and the expression of NF45 was correlated with tumor size (p = 0.007), histological differentiation (p = 0.033), and TNM stage (p = 0.001). Importantly, patients with low levels of NF45 expression exhibited better postoperative prognosis as compared with those with high NF45 expression. Furthermore, using PDAC cell cultures, we found that interference of NF45 expression using siRNA oligos suppressed PDAC cell proliferation and retarded cell cycle progression. Moreover, depletion of NF45 impaired the levels of cellular cyclin E and proliferating cell nuclear antigen (PCNA). Conversely, overexpression of NF45 facilitated the cell growth and accelerated cell cycle progression. Our results establish NF45 as an important indicator of PDAC prognosis with potential utility as a therapeutic target in this lethal disease.

MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma

“…It has been reported that ILF2 is abundantly expressed in pancreatic carcinoma (8) and it functions as an oncogene. Thus, we aimed to elucidate the mechanisms underlying the increased ILF2 expression in pancreatic carcinoma.…”

“…Thus, ILF2 may be a potential therapeutic target (8). Yet, the regulatory mechanisms of ILF2 remain largely elusive.…”

“…We found that miR-7 suppressed ILF2 protein expression and inhibited the proliferation, colony formation, migration and invasion as well as negatively regulated EMT-associated gene expression in PANC-1 cells. It has been reported that ILF2 is markedly upregulated in pancreatic carcinoma (8). Our results further demonstrated that miR-7 was significantly downregulated in pancreatic tissues, implying that ILF2 upregulation may be due to the lack of miR-7.…”

“…ILF2 is ubiquitously expressed in human tissues, especially the brain, thymus, pancreas, kidney and testis indicating that it is involved in the physiology of various cell types (4). ILF2 has been reported to promote the progression of multiple cancer types including cervical cancer, esophageal squamous cell carcinoma, glioma, pancreatic carcinoma and non-small cell lung cancer (5–8). Yet, the regulatory mechanisms of ILF2 remain largely elusive.…”

Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2and NF90/ILF3

“…disruption of NF90 and NF45 impaired ESC proliferation and promoted differentiation to an epiblast-like state (27). NF90 and NF45 regulate cell cycle progression (18,19,28), cell growth and proliferation (28)(29)(30)(31)(32)(33), and are amplified, overexpressed and mutated in diverse cancers (34,35).…”