Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC)

Abstract

NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients' poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression.

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

“…Therefore, NF45 may possess oncogenic property in the development of various cancer types. Furthermore, a recent report identified a close correlation between NF45 expression and tumor stage in esophageal squamous cell carcinoma (ESCC) and that NF45 was an independent prognostic factor for ESCC patients' poor survival [13]. In keeping with these findings, we found that NF45 expression was significantly associated with tumor size (p = 0.007), histological differentiation (p = 0.033), and TNM stage (p = 0.001).…”

“…In agreement with the data, we showed that high NF45 expression was observed in pancreatic ductal adenocarcinoma, whereas low expression was noted in normal pancreas. In addition to pancreatic cancer, NF45 has been reported to be overexpressed in glioma, cervical cancer, and esophageal cancer [11][12][13]. Therefore, NF45 may possess oncogenic property in the development of various cancer types.…”

“…Furthermore, NF45 is involved in the replication of some types of RNA viruses, such as hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV) [9,10]. NF45 has been documented to be overexpressed in lymphoma, leukemia, glioma, cervical cancer, and esophageal cancer, and may contribute to uncontrolled proliferation of cancer cells [7,[11][12][13]. Abolition of NF45-NF90 complex may facilitate the apoptosis of HeLa cells through modulating HPV-dependent p53 activation [12].…”

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

“…Some other studies have reported higher expression of hnRNP‐B1 (Matsuyama et al, ) and ‐H1 (Sun, Liu, Liu, & Zhao, ), NF45 (Ni et al, ), insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP)‐2 (Barghash, Golob‐Schwarzl, Helms, Haybaeck, & Kessler, ) and ‐3 (W. Feng et al, ; Kazeminezhad, Mirafsharieh, Dinyari, Azizi, & Ebrahimi, ; Trivedi, Cartun, & Ligato, ), DEAD‐Box Helicase 46 (B. Li, Li, et al, ), and Musashi‐1 (Mokrowiecka et al, ) in EC tissues. Because enhanced expression of these molecules was correlated with poor pathologic features and worse survival of patients, they are thought to be useful as new prognostic markers and potential anticancer targets in EC.…”

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

“…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.…”