<p>Epstein-Barr virus-encoded LMP1 regulated Pim1 kinase expression promotes nasopharyngeal carcinoma cells proliferation</p>

Abstract

Background Epstein–Barr virus-encoded LMP1 plays a critical role in the carcinogenesis of nasopharyngeal carcinoma (NPC), but the mechanism remains elusive. We aimed to analyze the expression and clinical pathological significance of provirus integration site for Moloney murine leukemia virus 1 (Pim1) in clinical NPC, and to elucidate the effect of LMP1 on Pim1 expression and its mechanism. Methods Immunohistochemical staining was used to detect the expression of Pim1 in clinical NPC tissues and control nasopharyngeal chronic inflammation (NPI) tissues, and the correlation between Pim1 and clinical parameters of NPC patients was analyzed. The LMP1 stable expression cell line CNE1-LMP1-OV was constructed through infecting the well-differentiated nasopharyngeal carcinoma cells CNE1 with LMP1 overexpressing lentivirus. Then the in vivo experiments were conducted. Results Among 89 NPC patients, 48 cases (53.93%) were positive for Pim1, while only one case was Pim1 positive in 15 NPI controls (6.67%). Pim1 expression was not correlated with gender, age, smoking status and clinical classification of NPC patients, but positively correlated with T, N and M classification. CNE1-LMP1-OV cell line was successfully established, which displayed a higher cell proliferation ability and Pim1 expression. NF-κB inhibitor PDTC, PKC inhibitor GF109203X and STAT3 inhibitor Stattic significantly attenuated LMP1-induced Pim1 expression, and while AP-1 inhibitor SR11302 showed no inhibitory effect. Interestingly, Pim1 inhibitor quercetagetin significantly inhibited the proliferation of CNE1-LMP1-OV cells. Conclusion LMP1 mediates Pim1 expression through NF-κB, PKC and STAT3 signaling, which promotes the proliferation of NPC cells and participate in the clinical progression of NPC.

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…Quercetagetin, an inhibitor of Pim1, can significantly inhibit the proliferation activity of NPC cells that express LMP1. 109 In the view of the key role of inhibitor of NF-κB kinase (IKK) in the activation of the NF-κB pathway, IKK inhibitor is considered as one of the strategies of targeted therapy for cancer. 110 The natural flavonoid glycoside vitexin can inhibit the activity of IKK thereby inhibiting the activation of the NF-κB signal pathway and inducing NPC cell apoptosis.…”

“…Quercetagetin, an inhibitor of Pim1, can significantly inhibit the proliferation activity of NPC cells that express LMP1. 109 …”

“…A quintessential example should be cited that is LMP1, which may contribute to the development of NPC through the STAT3 signal pathway. Ding et al 109 revealed that LMP1 can promote the activation of STAT3, protein kinase C (PKC), NF-κB, and AP1 in EBV-associated NPC cell NPC cells, thus activating Pim1 and promoting the proliferation of NPC cells.…”

Knockdown of LncRNA PANDAR by CRISPR-dCas9 Decreases Proliferation and Increases Apoptosis in Oral Squamous Cell Carcinoma

“…MicroRNA-33a silencing increases cyclin-dependent kinase 6, cyclin D1, and PIM1 expression and promotes cell proliferation in gastric cancer (Wang et al, 2015). Epstein-Barr virus-encoded LMP1 regulates Pim1 kinase expression to promote proliferation of cancer cells ( Ding et al, 2019 ). Physcion 8-O-β-glucopyranoside represses tumor growth of hepatocellular carcinoma via downregulation of PIM1 ( Wang et al, 2017 ).…”

LMP1 Up-regulates Calreticulin to Induce Epithelial-mesenchymal Transition via TGF-β/Smad3/NRP1 Pathway in Nasopharyngeal Carcinoma Cells

“…Recurrence and metastasis are the main causes of death in patients with NPC 1 . The occurrence of NPC is associated with Epstein-Barr virus (EBV) infection, and EBV-encoded Latent membrane protein 1 (LMP1) promotes Ivyspring International Publisher proliferation, migration and invasion of NPC cells [2][3][4][5] . LMP1 is known to be a vital oncogenic protein encoded by the EBV genome, as it plays a critical role in the transformation of rodent fibroblasts and some immortalized epithelial cells in vitro [6][7] .…”