LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma

Li, Yuan; Song, Shumei; Pizzi, Melissa Pool; Han, Guangchun; Scott, Ailing W.; Jin, Jiankang; Xu, Yan; Wang, Ying; Huo, Longfei; Ma, Lang; Vellano, Christopher P.; Luo, Xiaolin; MacLeod, Robert A.; Wang, Linghua; Wang, Zhenning; Ajani, Jaffer A.

doi:10.3390/cancers12102995

Cited by 20 publications

(12 citation statements)

References 47 publications

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“…Silencing of PVT1 by ASOs significantly inhibits the growth and invasion of GC cells. 184 Moreover, the CRISPR-Cas9 genome editing technique has been recognized as a potential therapeutic tool for cancer treatment by reactivating or silencing lncRNAs. For instance, GC metastasis associated long non-coding RNA (GMAN) can be disrupted by CRISPR-Cas9 through deleting the MFR region of GMAN, leading to downregulation of GC cell invasive activity.…”

Section: Clinical Implications Of Lncrnas In Gcmentioning

confidence: 99%

Long non-coding RNAs: Biogenesis, functions, and clinical significance in gastric cancer

Liu

Ding

et al. 2021

Molecular Therapy - Oncolytics

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Gastric cancer (GC) is one of the most prevalent malignant tumor types and the third leading cause of cancer-related death worldwide. Its morbidity and mortality are very high due to a lack of understanding about its pathogenesis and the slow development of novel therapeutic strategies. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with a length of more than 200 nt. They play crucial roles in a wide spectrum of physiological and pathological processes by regulating the expression of genes involved in proliferation, differentiation, apoptosis, cell cycle, invasion, metastasis, DNA damage, and carcinogenesis. The aberrant expression of lncRNAs has been found in various cancer types. A growing amount of evidence demonstrates that lncRNAs are involved in many aspects of GC pathogenesis, including its occurrence, metastasis, and recurrence, indicating their potential role as novel biomarkers in the diagnosis, prognosis, and therapeutic targets of GC. This review systematically summarizes the biogenesis, biological properties, and functions of lncRNAs and highlights their critical role and clinical significance in GC. This information may contribute to the development of better diagnostics and treatments for GC.

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Section: Clinical Implications Of Lncrnas In Gcmentioning

confidence: 99%

Long non-coding RNAs: Biogenesis, functions, and clinical significance in gastric cancer

Liu

Ding

et al. 2021

Molecular Therapy - Oncolytics

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“…Extensive studies have demonstrated that lncRNA PVT1 was a carcinogenic RNA (14). Li et al concluded that the expression of lncRNA PVT1 highly correlated with the poor prognoses of patients with gastric adenocarcinoma (15). Lu et al concluded that PVT1 regulated ferroptosis mediated by miR-214 (16).…”

Section: Discussionmentioning

confidence: 99%

“…Li et al. concluded that the expression of lncRNA PVT1 highly correlated with the poor prognoses of patients with gastric adenocarcinoma ( 15 ). Lu et al.…”

Section: Discussionmentioning

confidence: 99%

The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma

Chen

Zhu

et al. 2021

Front. Oncol.

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BackgroundFerroptosis is a new type of cell death different from apoptosis, necrosis, autophagy, and pyroptosis. This study aimed to explore the relationship between ferroptosis-related noncoding RNA (ncRNA) and gastric adenocarcinoma with regard to immunity and prognosis.MethodsFerroptosis-related ncRNA expression profiles and clinical pathology and overall survival information were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. The ferroptosis-related ncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The survival analysis, receiver operating characteristic (ROC) analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. The correlation between risk and multiple clinical characteristics was analyzed using the chi-square test. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for mining functions and pathways. The CIBERSORT, ssGSEA, and ESTIMATE algorithms were used to assess immune infiltration and the tumor microenvironment. The response of immunotherapy was predicted using the Submap algorithm, and the Connectivity Map and the ridge regression model were used to screen and evaluate drugs.ResultsA carcinogenic risk signature was constructed using five ferroptosis-related ncRNAs. It showed an extraordinary ability to predict the prognoses of patients with gastric adenocarcinoma [area under the ROC curve (AUC) after 6 years = 0.689; GSE84426, AUC after 6 years = 0.747]. The lower ferroptosis potential level and lower tumor mutation burden were related to the poor prognoses of patients. The high-risk group had more immune cell recruitment, and the overall effect of the anti-immune checkpoint immunotherapy was not as good as that of the low-risk group. The high- and low-risk groups were enriched in tumor- and immune-related pathways, respectively. The screened antitumor drugs, such as genistein, guanabenz, and betulinic acid, improved the survival of the patients.ConclusionsThe ferroptosis-related ncRNA signature is a potential carcinogenic prognostic biomarker of gastric adenocarcinoma.

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“…Among the eight prognostic ferroptosis-related lncRNAs (AL365181.3, MIR3142HG, PVT1, LINC01315, AL353804.1, HAGLR, AC005586.1, and AC245041.1) found in GC, PVT1 was signi cantly upregulated in gastric adenocarcinoma (GAC) compared to matched adjacent normal tissues. Its expression level was positively correlated with larger tumor size, deeper wall invasion, lymph node metastases, and short survival duration, indicating that PVT1 is a poor prognosticator as well as a therapeutic target in GAC (25). It is also a poor prognosticator of esophageal adenocarcinoma (EAC) as its expression was upregulated in EAC compared to paired Barrett's esophagus and normal esophageal tissues.…”

Section: Discussionmentioning

confidence: 99%

A Novel Ferroptosis-Related Long Non-coding RNA Prognostic Risk Model for Gastric Cancer

Huang

Zhuang

et al. 2021

Preprint

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Background：Gastric cancer (GC) is one of the most common malignant tumors with a poor prognosis. Ferroptosis is a novel and distinct type of non-apoptotic cell death that is closely associated with metabolism, redox biology, and tumor prognosis. Recently, ferroptosis-related long non-coding RNAs (lncRNAs) have received increasing attention in predicting cancer prognosis. Thus, we aimed to construct an ferroptosis-related lncRNAs signature for predicting the prognosis of patients with gastric cancer.Methods：We built an ferroptosis-related lncRNA risk signature by using Cox regression based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. Cox regression was performed to explore whether the signature could be used as an independent factor. A nomogram was built involving the risk score and clinicopathological features. Furthermore, we explored the biological functions and immune states in two groups.Results：Eight ferroptosis-related lncRNAs were obtained for constructing the prognosis model in gastric cancer. Kaplan–Meier curve analysis revealed that patients in the high-risk group had worse survival than those in the low-risk group. The survival outcome was also appropriate for subgroup analysis, including age, sex, grade, and clinical stage. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis demonstrated that the risk score was an independent prognostic factor and superior to traditional clinicopathological features in predicting GC prognosis. Next, we established a nomogram according to clinical parameters (age, sex, grade, and clinical stage) and risk score. All the verified results, including ROC curve analysis, calibration curve, and decision curve analysis, demonstrated that the nomogram could accurately predict the survival of patients with gastric cancer. Gene set enrichment analysis revealed that these lncRNAs were mainly involved in cell adhesion, cancer pathways, and immune function regulation.Conclusion: We established a novel ferroptosis-related prognostic risk signature including eight lncRNAs and constructed a nomogram to predict the prognosis of gastric cancer patients, which may improve prognostic predictive accuracy and guide individualized treatment for patients with GC.

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LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma

Cited by 20 publications

References 47 publications

Long non-coding RNAs: Biogenesis, functions, and clinical significance in gastric cancer

Long non-coding RNAs: Biogenesis, functions, and clinical significance in gastric cancer

The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma

A Novel Ferroptosis-Related Long Non-coding RNA Prognostic Risk Model for Gastric Cancer

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