&lt;p&gt;Paip1 overexpression is involved in the progression of gastric cancer and predicts shorter survival of diagnosed patients&lt;/p&gt;

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

“…However, in lymphocytes, an inverse correlation between miR-340 and PAIP1 protein expression was detected, suggesting that PAIP1 expression might be regulated by miR-340. PAIP1 is a key promoter of translation, mainly studied in cancer contexts and never evaluated before in GDM [75]. Human lymphocytes were cultured in high glucose, reproducing in vitro fasting and after meal glycaemia.…”

Section: Insulin Resistance and Metabolic Adaptationsmentioning

confidence: 99%

Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications

Filardi

Catanzaro

Mardente

et al. 2020

IJMS

Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance that develops in the second or third trimester of pregnancy. GDM can lead to short-term and long-term complications both in the mother and in the offspring. Diagnosing and treating this condition is therefore of great importance to avoid poor pregnancy outcomes. There is increasing interest in finding new markers with potential diagnostic, prognostic and therapeutic utility in GDM. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, are critically involved in metabolic processes and their dysregulated expression has been reported in several pathological contexts. The aberrant expression of several circulating or placenta-related ncRNAs has been linked to insulin resistance and β-cell dysfunction, the key pathophysiological features of GDM. Furthermore, significant associations between altered ncRNA profiles and GDM-related complications, such as macrosomia or trophoblast dysfunction, have been observed. Remarkably, the deregulation of ncRNAs, which might be linked to a detrimental intrauterine environment, can lead to changes in the expression of target genes in the offspring, possibly contributing to the development of long-term GDM-related complications, such as metabolic and cardiovascular diseases. In this review, all the recent findings on ncRNAs and GDM are summarized, particularly focusing on the molecular aspects and the pathophysiological implications of this complex relationship.

“…There are a few reasons to assume PAIP1 is a regulator in gallbladder tumors acting via PLK1. First, it has been reported that PAIP1 exerts its tumor-promoting role by facilitating cell cycle progression through regulating the expression of cyclin D1 in gastric cancer (14). Researchers have shown that PAIP1 knockdown results in decreased expression of cyclin D1, whereas overexpression of PAIP1 enhances its expression.…”

Section: Discussionmentioning

confidence: 99%

“…Intriguingly, an abnormally high expression of PAIP1 has been demonstrated to be linked with poor overall survival in various human cancers, including breast, gastric, liver, pancreatic, and lung cancers (12)(13)(14)(15)(16). For example, using different tissue-derived cell lines, Lin group has shown that overexpression of PAIP1 promotes cell proliferation, metastasis, and angiogenesis, whereas knockdown of PAIP1 inhibits these phenotypes, in both breast and pancreatic cancers, suggesting its pathological roles in tumorigenesis (12).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of PAIP1 promotes the gallbladder tumorigenesis through regulating PLK1 level

Bi¹,

Ma²,

Liu³

et al. 2021

Ann Transl Med

Background: Increasing evidence suggests that elevated expression of polyA-binding protein-interacting protein 1 (PAIP1) is associated with cancer development and progression. However, how PAIP1 promotes gallbladder cancer (GBC) is still unclear.Methods: Two GBC tissue-derived cell lines, NOZ and GBC-SD cells, were used in this study. Assays of cell proliferation, colony formation, apoptosis, and xenograft tumor model were performed to examine the tumorigenic effects of PAIP1. Immunohistochemical (IHC) staining was used to examine the expression level of PAIP1 in both patient GBC tissues and mouse tumors. Microarray and bioinformatics analysis were used to explore the targets of PAIP1. Quantitative polymerase chain reaction (qPCR) and western blot analysis were used to validate PAIP1-mediated targets.Results: We found that upregulated PAIP1 expression was correlated with GBC. Knockdown of PAIP1 in gallbladder cells alleviated cell proliferation, promoted apoptosis, and inhibited xenograft tumor growth.Gene microarray analysis showed that stable silencing of PAIP1 altered various gene expressions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that PAIP1 regulates cell cycle progression. Finally, we found that the PLK1 kinase, a key regulator of cell cycle, was regulated by PAIP1 at the transcriptional and protein levels. PLK1 level was positively correlated with PAIP1 level in both mouse tumors and GBC tissues. PAIP1 interacted with PLK1, and rescue of PAIP1 could recover PLK1 protein level and inhibit apoptosis.Conclusions: Our data suggest that PAIP1 contributes to GBC progression likely through regulating PLK1 level. Since upregulated PAIP1 expression is positively associated with GBC, PAIP1 may act as a clinical prognostic biomarker of GBC.