PNO1, which is negatively regulated by miR-340-5p, promotes lung adenocarcinoma progression through Notch signaling pathway

Abstract

Many studies have shown that the hyperactivation of ribosome biogenesis plays essential roles in the initiation and progression of cancers. As a ribosome assembly factor, PNO1 plays an important role in ribosome biogenesis. However, little is known about the expression and function of PNO1 in human tumors. In our present study, we aimed to explore the functional roles and the underlying molecular mechanisms of PNO1 in human lung adenocarcinoma (LUAD). Both bioinformatics databases and tumor tissues demonstrated that the expression of PNO1 in LUAD tissues was higher than that in adjacent tissues and predicted poor survival in LUAD patients. In vitro and in vivo assays suggested that downregulation of PNO1 expression suppressed LUAD cell proliferation and invasion. Further studies found that miR-340-5p depressed PNO1 expression via direct binding to the 3′ untranslated region (UTR) of PNO1. PNO1 expression was negatively correlated with miR-340-5p expression in LUAD cells and tissue samples. Moreover, upregulation or downregulation of miR-340-5p expression reversed the effects of PNO1 inhibition and overexpression, respectively. Meanwhile, downregulation of PNO1 inhibited Notch signaling pathway which modulated epithelial mesenchymal transition (EMT). These results indicate that PNO1, negatively regulated by miR-340-5p, played an important role in LUAD progression via Notch signaling pathway. The miR-340-5p/PNO1/Notch axis might be a potential target for individualized and precise treatment of LUAD patients in the future.

RETRACTED ARTICLE: MYC-mediated upregulation of PNO1 promotes glioma tumorigenesis by activating THBS1/FAK/Akt signaling

“…Several studies have proven that PNO1 acts as an essential role in tumorigenesis and development; [24][25][26][27] however, its role in glioma remains poorly defined. In this study, we provided evidence from clinical specimens and glioma cell lines that PNO1, driven by the transcription factor MYC, significantly contributes to glioma cell proliferation and metastasis via regulating the expression of THBS1, leading to the phosphorylation of FAK and Akt (Fig.…”

PNO1 promotes human cholangiocarcinoma tumorigenesis and chemosensitivity

“…For example, Peng revealed that mammalian PNO1 worked as a ribosome assembly factor in colorectal cancer cells, and its oncogenic effects could serve as a novel therapeutic strategy in colorectal cancer [14]. Guo offered the evidence that PNO1, a direct functional target of miR-340-5p, was related with Notch pathway and EMT, which acts as promising target for the treatment of lung adenocarcinoma in the future [16]. In the present study, we found that PNO1 was upregulated in CHOL tissues and knockdown the expression of PNO1 could inhibit RBE cell growth in vitro, which might be predictive of the potential of PNO1 as a prognostic biomarker and its oncogenic effects in CHOL progression.…”

“…It is responsible for the cleavage of 18S mediated by binding to NOB1, while its deletion could inhibit the synthesis of 18S rRNA and 40S subunit [12,13]. In addition to the numerous studies of ribosome-related function of PNO1, several studies have reported that PNO1 acts as an oncogene in cancer cells, including colorectal cancer, lung adenocarcinoma and urinary bladder carcinoma [14][15][16]. Therefore, exploring the relationship between PNO1 and CHOL is essential to the future exploration of new targeted therapies.…”

Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study

“…IHC staining was used to examine the expression levels of AFU in paraffin-embedded samples of HCC tissues according to previously described methods 31 . An anti-AFU (FUCA2) antibody was purchased from Bioss (bs-16192R, 1:200; Bioss, Woburn, MA, USA).…”