NKAP plays an oncogenic function partly through AKT signaling pathway in hepatocellular carcinoma

Abstract

NF-κB activating protein (NKAP) is a highly conserved protein involved in transcriptional repression, immune cell development, maturation, T cell acquisition of functional competency and maintenance of hematopoiesis. Here, we first explore the function of NKAP in hepatocellular carcinoma (HCC). We found that NKAP was highly expressed in HCC tissues and associated with a poor patient survival. CCK8 assay showed that NKAP knockdown significantly decreased cell viability of HuH7 and Hep3B HCC cell lines. Cell invasion, tested by transwell assays, was significantly inhibited by NKAP knockdown in HuH7 and Hep3B cells (p<0.05). Percentage of cell apoptosis was significantly increased by NKAP knockdown in HuH7 cells (6.5% to 12.5%) and in Hep3B cells (8.3% to 27.3%). Furthermore, western blot results indicated that NKAP silencing upregulated the expression of pro-apoptotic proteins Bax and Caspase3-P17 while downregulated anti-apoptotic protein Bcl2. Finally, AKT signaling pathway was evaluated to reveal the underlying mechanism of NKAP in HCC cells. It was suggested that NKAP knockdown decreased the phosphorylation level of AKT and the expression of its downstream members p70S6K and Cyclin D1. Furthermore, we demonstrated that NKAP knockdown also played an oncogenic role in human gastric cancer AGS and MKN45 cells. In conclusion, our study for the first time reveals that NKAP promotes the proliferation and invasion in HCC cell lines at least partly through AKT signaling pathway.

Triacontanoic ester of 5ʹʹ-hydroxyjustisolin: Tumour suppressive role in cervical cancer via Bcl-2, BAX and caspase-3 mediated signalling

“…The antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic proteins (BAX, Bid and Caspases). The BAX/Bcl-2 ratio is considered a measure of cell susceptibility to apoptosis [28] as well as proapoptotic index [29]. This ratio was found to be significantly decreased in the current study as reported earlier and may be due to the increased apoptosis via increasing proapoptotic Bax and decreasing antiapoptotic Bcl-2 expression in an animal model [30,31].…”

The functional roles, cross-talk and clinical implications of m6A modification and circRNA in hepatocellular carcinoma

“…NKAP was highly expressed in HCC tissues. And NKAP promoted the proliferation and invasion in HCC cell through AKT signaling pathway [40]. Zhao et al discovered that YTHDF1 was significantly upregulated in HCC and positively related to pathological stage.…”

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

“…FADD association with NKAP in the nucleus would stabilize the latter, therefore contributing to its role as a transcriptional repressor able to hamper NOTCH-mediated transcriptional activation. High levels of NKAP have been observed in most tumor types (), and it has been described as an oncogene in hepatocellular carcinoma [141], glioma [142], and breast cancer [143], even as an unfavorable prognostic indicator in the latter (). FADD downregulation in certain cancer types—such as T-LBL—might result in the reduced stability of NKAP complexes in the nucleus, contributing to NOTCH hyperactivation frequently found in T-cell lymphoblastic neoplasms [144].…”