MERIT: Systematic Analysis and Characterization of Mutational Effect on RNA Interactome Topology

Li, Yongsheng; McGrail, Daniel J.; Xu, Juan; Li, Junyi; Liu, Ning Ning; Sun, Ming; Lin, Richard Z.; Pancsa, Rita; Zhang, Jiwei; Lee, Ju Seog; Wang, Hui; Mills, Gordon B.; Li, Xia; Yi, S. Stephen; Sahni, Nidhi

doi:10.1002/hep.30242

Cited by 24 publications

(23 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have suggested that dysregulation of multiple RNAs is involved in the development and progression of HCC and could act as a risk predictor of HCC patient survival . This indicates the possible importance of RNA‐binding proteins (RBP), key posttranscriptional regulators that control the fate of nearly every RNA transcript in a cell, in HCC ; indeed, aberrant expression of RBP is observed in human cancers, including HCC, and plays a prominent role in the development and progression of HCC by inducing dysregulation of the HCC transcriptome . Therefore, in‐depth research on the dysregulation of the multiple RNAs mediated by RBP will aid in better understanding RBP‐RNA interaction networks in HCC, which is anticipated to provide valuable insights into early diagnostic biomarkers and reliable therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have suggested that dysregulation of multiple RNAs is involved in the development and progression of HCC and could act as a risk predictor of HCC patient survival [7,8]. This indicates the possible importance of RNA-binding proteins (RBP), key posttranscriptional regulators that control the fate of nearly every RNA transcript in a cell, in HCC [7][8][9][10]; indeed, aberrant expression of RBP is observed in human cancers, including HCC, and plays a prominent role in the development and progression of HCC by inducing dysregulation of the HCC transcriptome [7][8][9][10]. Therefore, in-depth research on the dysregulation of the multiple 396 H Kang, S Heo et al Polypyrimidine tract-binding protein 1 (PTBP1), also known as heterogeneous nuclear ribonucleoprotein (hnRNP) I, is one of the most investigated multifunctional RBP, regulating several biological processes including cell structure and motility, protein metabolism and modification, immunity, and the cell cycle [11,12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A miR‐194/PTBP1/CCND3 axis regulates tumor growth in human hepatocellular carcinoma

Kang

Heo

Shin

et al. 2019

The Journal of Pathology

View full text Add to dashboard Cite

Polypyrimidine tract‐binding protein 1 (PTBP1) is one of the most investigated multifunctional RNA‐binding proteins (RBP), controlling almost all steps of mRNA metabolism and processing. It has been reported that PTBP1 is overexpressed in many different types of cancer and this high expression is associated with increased proliferation and poor prognoses. However, there are no reports on a putative role for PTBP1 in the molecular abnormalities and pathogenesis of hepatocellular carcinoma (HCC). Here, we identified PTBP1 as a positive regulator of human HCC growth. The expression of PTBP1 was increased in human HCC cells and tissues compared to the corresponding controls, and this high expression was positively correlated with increased tumor size and a reduced survival rate. Mechanistically, PTBP1 enhanced cyclin D3 (CCND3) translation by interacting with the 5′‐untranslated region (5′‐UTR) of CCND3 mRNA, consequently facilitating cell cycle progression and tumor growth. Furthermore, we found that miR‐194 inhibits PTBP1 expression by binding to the 3′‐UTR of PTBP1 mRNA, resulting in reduced CCND3 levels and HCC cell growth; moreover, the levels of PTBP1 were negatively correlated with miR‐194 levels in HCC. Taken together, these findings identify PTBP1 as a pivotal enhancer of HCC growth; the miR‐194/PTBP1/CCND3 axis seemingly has a crucial role in the development and progression of HCC and targeting the axis could be a novel therapeutic strategy against human HCC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Recent studies have suggested that dysregulation of multiple RNAs is involved in the development and progression of HCC and could act as a risk predictor of HCC patient survival [7,8]. This indicates the possible importance of RNA-binding proteins (RBP), key posttranscriptional regulators that control the fate of nearly every RNA transcript in a cell, in HCC [7][8][9][10]; indeed, aberrant expression of RBP is observed in human cancers, including HCC, and plays a prominent role in the development and progression of HCC by inducing dysregulation of the HCC transcriptome [7][8][9][10]. Therefore, in-depth research on the dysregulation of the multiple 396 H Kang, S Heo et al Polypyrimidine tract-binding protein 1 (PTBP1), also known as heterogeneous nuclear ribonucleoprotein (hnRNP) I, is one of the most investigated multifunctional RBP, regulating several biological processes including cell structure and motility, protein metabolism and modification, immunity, and the cell cycle [11,12].…”

Section: Introductionmentioning

confidence: 99%

A miR‐194/PTBP1/CCND3 axis regulates tumor growth in human hepatocellular carcinoma

Kang

Heo

Shin

et al. 2019

The Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…The mutational spectrum of RBPs had been analyzed and identified a number of RBPs exhibited significantly mutation in cancer (Neelamraju et al, 2018). Li et al, have also decoded the genome-wide RBP mutational and transcriptomic landscape and yielded valuable insights into the function of RBPs (Li et al, 2019a). All these results suggest that there are prevalent alterations of RBPs in cancer development and progression.…”

Section: Introductionmentioning

confidence: 99%

Systematically Dissecting the Function of RNA-Binding Proteins During Glioma Progression

Wang

Hou

2020

Front. Genet.

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) play important roles in regulating gene expression and dysregulation of RBPs have been observed in various types of cancer. However, the role of RBPs during glioma progression, and particular in Chinese patients, is only starting to be unveiled. Here, we systematically analyzed the somatic mutation, gene expression patterns of 2949 RBPs during glioma progression. Our comprehensive study reveals several of highly mutated genes (such as ATRX, TTN and SETD2) and differentially expressed genes (such as KIF4A, TTK and CEP55). Integration of the expression of RBPs and genes, we constructed a regulatory network in glioma and revealed the functional links between RBPs and cancer-related genes. Moreover, we identified the prognosis spectrum of RBPs during glioma progression. The expression of a number of RBPs, such as SNRPN and IGF2BP3, are significantly associated with overall survival of patients in all grades. Taken together, our analyses provided a valuable RBP resource during glioma progression, and revealed several candidates that potentially contribute to development of therapeutic targets for glioma.

show abstract

“…Due to the unobtrusive nature of the symptoms, nearly 75% of patients present at an advanced stage, leading to a 5-year-survival rate of only 29% in the advanced stage. The rst-line therapy is tumor-debulking surgery followed by platinum-based chemotherapy; however, recurrence occurs in nearly 75% of patients 2 . Moreover, there is no con rmed effective drug for patients following platinum-resistant recurrence.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a prognostic model based on immune infiltration-related genes and clinical information in ovarian cancer

Kong¹,

Zhang²,

Gao³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Ovarian cancer is one of the most lethal gynecological cancers,and is in the top five cancer types associated with death in women. Immune infiltration of ovarian cancer is a critical factor in determining patient's prognosis. In addition to immune infiltration, key mutations also have a greater impact on the development and prognosis of OV.Methods Using data from TCGA and GTEx database combined with WGCNA and ESTIMATE methods, genes related to OV occurrence and immune infiltration were identified. Lasso and multivariate Cox regression were applied to define a prognostic score (IGCI score) based on immune genes and clinical information. The IGCI score has been verified by K-M curves, ROC curves, C-index on test set. Based on mutation data from TCGA, we identified key mutations related to immune infiltration by Chi-squared tests and we also did survival analysis of these mutations.Results In this section, we found 46 genes related to disease occurrence and immune infiltration, IGCI score was established based on six factors: Age, White, Pharmaceutical, FGF7, CCR1 and CD14. In test set, IGCI score (C-index = 0.630) is significantly better than AJCC stage (C-index = 0.541, P < 0.05) and CIN25 (C-index = 0.571, P < 0.05). Chi-squared tests revealed that 6 mutations are significantly (P < 0.05) related to immune infiltration : BRCA1, ZNF462, VWF, RBAK, RB1, and ADGRV1. According to mutation survival analysis, we found another 5 key mutations significantly related to patient prognosis (P < 0.05): CSMD3, FLG2, HMCN1, TOP2A, TRRAP. RB1 and CSMD3 mutations had small p-value (P < 0.1) in both Chi-squared tests and survival analysis. Then we conducted a drug sensitivity analysis of key mutation and found when RB1 mutation occurs, the efficacy of six anti-tumor drugs has changed significantly (P < 0.05).Conclusion Based on immune-related genes and clinical information, we have established an ovarian cancer prognosis score that is superior to other methods. At the same time, RB1 and CSMD3 gene mutations are considered to be closely related to ovarian cancer immunity and prognosis.

show abstract

MERIT: Systematic Analysis and Characterization of Mutational Effect on RNA Interactome Topology

Cited by 24 publications

References 43 publications

A miR‐194/PTBP1/CCND3 axis regulates tumor growth in human hepatocellular carcinoma

A miR‐194/PTBP1/CCND3 axis regulates tumor growth in human hepatocellular carcinoma

Systematically Dissecting the Function of RNA-Binding Proteins During Glioma Progression

Establishment of a prognostic model based on immune infiltration-related genes and clinical information in ovarian cancer

Contact Info

Product

Resources

About