Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3β pathway in lung adenocarcinoma

Jung

et al. 2020

In Vivo

Background/Aim: Translation plays an important role in the carcinogenesis of various human tumors. Paip1 and eIF4A1 are translation-associated proteins that mediate the function of eukaryotic initiation factor 4F complex. This study aimed to analyse the relationship between the expression status of Paip1 and eIF4A1 and clinicopathologic features in hepatocellular carcinoma (HCC). Materials and Methods: Immunohistochemical analysis was used to evaluate the expression status of Paip1 and eIF4A1. Two pathologists independently interpreted the immunostained slides. The prognostic value of Paip1 and eIF4A1 was evaluated by the Kaplan-Meier plotter. Results: Among 173 HCC patients, 28 (16.1%) and 46 (26.6%) belonged in the Paip1 and eIF4A1 high-expression groups. High expression of Paip1 and eIF4A1 was associated with advanced TNM stage and more frequent vascular tumor invasion. Univariate analysis indicated that high Paip1 expression was associated with worse five-year overall survival (OS). Public dataset analysis by Kaplan-Meier plotter revealed that high mRNA expression of Paip1, and not of eIF4A1, was significantly associated with worse five-year OS and disease-free survival. Conclusion: Paip1 expression has a potential prognostic value in human HCC.Translation is one of the core processes in posttranscriptional gene expression regulation and is an important factor in tumorigenesis (1, 2). The eIF4F complex is involved in eukaryote translation initiation and consists of eIF4E, eIF4G, and eIF4A. Poly (A)-binding protein (PABP) binds to eIF4G to induce mRNA circularization and stimulate mRNA translation. Poly (A)-binding proteininteracting protein 1 (Paip1) is encoded by the PAIP1 gene and binds to PABP to regulate its activity (3). High expression of Paip1 has been reported to be associated with poor overall survival in various tumors, including gastric, breast, pancreatic, uterine, and cervical cancers (4-7).eIF4A1, which is one of three isoforms of eIF4A, is a constituent of the eIF4F complex and an ATP-dependent RNA helicase that plays a critical role in translation initiation by unwinding 5'-UTR structures of mRNA. Several reports suggest that eIF4A1 might be involved in the process of carcinogenesis (8-10).This study aimed to examine the levels of Paip1 and eIF4A1 proteins that regulate human translation initiation in hepatocellular carcinoma (HCC). We investigated their association with various clinicopathological parameters. In addition, we divided patients into low-and high-expression groups and analyzed whether there was a significant difference in survival.

Section: Discussionsupporting

confidence: 59%

High Paip1 Expression as a Potential Prognostic Marker in Hepatocellular Carcinoma

Jung

et al. 2020

In Vivo

“…15,17,21 In recent years, many researchers have reported that PAIP1 is highly expressed in various human tumors, such as breast cancer, 12 cervical cancer, 9,10 pancreatic cancer, 13 and lung adenocarcinoma. 22 The upregulation of PAIP1 protein was significantly correlated with high histological grade, advanced clinical stage, and poor survival.…”

Section: Discussionmentioning

confidence: 95%

“…The expression of PAIP1 related oncogene protein is regulated by various mechanisms, among which transfer‐related genes regulatory mechanisms have an impact on the rapid response of cells to microenvironmental changes 15,17,21 . In recent years, many researchers have reported that PAIP1 is highly expressed in various human tumors, such as breast cancer, 12 cervical cancer, 9,10 pancreatic cancer, 13 and lung adenocarcinoma 22 . The upregulation of PAIP1 protein was significantly correlated with high histological grade, advanced clinical stage, and poor survival.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of inducing apoptosis and inhibiting proliferation of siRNA on polyadenylate‐binding protein‐interacting protein 1 in tongue cell carcinoma

Xie

Yang

et al. 2020

Head & Neck

Background: It has been reported that the polyadenylate-binding proteininteracting protein 1 (PAIP1) pathway is closely connected with the progression of some malignant tumors. Here we examined the potential functional mechanism of PAIP1 in tongue squamous cell carcinoma (TSCC). Methods: PAIP1 was knocked down in TSCC cell lines and proliferation and apoptosis in vitro analyzed. The molecular features of TSCC were determined using quantitative proteome and succinylome analyses. The results were confirmed in the mouse model. Results: PAIP1 promoted cell proliferation and inhibited apoptosis. Its knockdown decreased Ki67 and Pcna expressions and increased Bax/Bcl2 index and Caspase-3 expression. Bioinformatics analysis for proteomics revealed that PAIP1 knockdown correlated with the changes in differential protein expression. Conclusions: Upregulation of PAIP1 induces cell proliferation and inhibits apoptosis in TSCC; PAIP1 might be a diagnostic biomarker and a significant drug target. K E Y W O R D S cell apoptosis, oral squamous cell carcinoma, PAIP1, tumor growth, RNAi 1 | INTRODUCTION Oral cancer, a common malignant tumor posing a serious threat to human life, is the sixth most common cancer worldwide. 1 Oral squamous cell carcinoma (OSCC) is the malignant tumor with the highest frequency in the oral cavity. The OSCC includes cancer of the lip, tongue, gingiva, buccal mucosa, the floor of the mouth, and palate. 1,2 Most OSCC may spread rapidly to involve lymph nodes and cause great damage. 3,4 Although advances in chemotherapy, radiotherapy, and surgery have been developed over the past decade for oral cancer,

J of Gastro and Hepatol

“…A cytoplasmic expression pattern was considered positive staining. Ezrin expression was scored according to staining intensity and the percentage of positive cells as previously described 18 . Briefly, staining intensity of tissue sections scored as “0” (no staining), “1” (weak staining), “2” (moderate staining), and “3” (intense staining).…”

Section: Methodsmentioning

confidence: 99%

Ezrin as a prognostic indicator regulates colon adenocarinoma progression through glycolysis

Wang

Yang

Wang

et al. 2020

Self Cite

Background and Aim Aerobic glycolysis (the Warburg effect) is a distinctive metabolic hallmark of colon adenocarcinoma. Ezrin was a member of the Ezrin–Radixin–Moesin protein family and has been found profoundly implicated in tumorigenesis. However, the specific functional roles of Ezrin in metabolic reprogramming of colon adenocarcinoma remain poorly characterized and need to be explored. Methods The expression of Ezrin in colon adenocarcinoma tissues was screened by bioinformatics analysis and immunohistochemical assay. Si‐RNA‐mediated transfection and overexpression plasmid transfection were performed in colon adenocarcinoma cells. The proliferation viability was measured using MTT, colony formation, and EdU assays. The migration ability was determined using wound healing and transwell assay. The expression of EMT markers and transcriptional factors was detected using immunofluorescence staining and western blot assays. Glucose uptake, lactate production, and ATP assay were performed to validate the effect of Ezrin on glycolysis‐mediated colon adenocarcinoma progression. Results Ezrin was upregulated in colon adenocarcinoma tissues and associated with poor survival. Ezrin stimulated colon adenocarcinoma cell proliferation, migration, and the process of EMT. Ezrin aroused significant increase in glucose uptake, lactate production, and ATP level in colon adenocarcinoma cells. Further investigations demonstrated that treatment with a glycolytic inhibitor 2‐deoxy‐d‐glucose reversed the effects reduced by Ezrin on colon adenocarcinoma cells. Conclusions Our results evidenced a novel mechanism for colon adenocarcinoma cells proliferation and migration induced by Ezrin via glycolysis.