lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis

Wu, Hao; Wei, Ming; Jiang, Xinglu; Tan, Jiacheng; Xu, Wei; Fan, Xuetong; Zhang, Rui; Ding, Chenbo; Zhao, Feng; Shao, Xinxing; Zhang, Zhigang; Shi, Ruihua; Zhang, Weijia; Wu, Guoqiu

doi:10.1016/j.omtn.2020.03.006

Cited by 79 publications

(62 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its aberrant expression can be a relatively independent regulatory factor for promoting tumorigenesis and MYC [ 22 , 23 , 24 ]. The upregulation of PVT1 suggests that it can be used for the early detection of cancer, the prognostication of drug resistance, or as a therapeutic target [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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

Song

Pizzi

et al. 2020

Cancers

View full text Add to dashboard Cite

Gastric adenocarcinoma (GAC) is inherently resistant or becomes resistant to therapy, leading to a poor prognosis. Mounting evidence suggests that lncRNAs can be used as predictive markers and therapeutic targets in the right context. In this study, we determined the role of lncRNA-PVT1 in GAC along with the value of inhibition of PVT1 using antisense oligos (ASOs). RNA scope in situ hybridization was used to analyze PVT1 expression in tumor tissue microarrays (TMAs) of GAC and paired normal tissues from 792 patients. Functional experiments, including colony formation and invasion assays, were performed to evaluate the effects of PVT1 ASO inhibition of PVT1 in vitro; patient-derived xenograft models were used to evaluate the anti-tumor effects of PVT1 ASOs in vivo. LncRNA-PVT1 was upregulated in GACs compared to the matched adjacent normal tissues in the TMA. LncRNA PVT1 expression was positively correlated with larger tumor size, deeper wall invasion, lymph node metastases, and short survival duration. Inhibition of PVT1 using PVT1 ASOs significantly suppressed tumor cell growth and invasion in vitro and in vivo. PVT1 expression was highly associated with poor prognosis in GAC patients and targeting PVT1 using PVT1 ASOs was effective at curtailing tumor cell growth in vitro and in vivo. Thus, PVT1 is a poor prognosticator as well as therapeutic target. Targeting PVT1 using PVT1 ASOs provides a novel therapeutic strategy for GAC.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Song

Pizzi

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…PVT1 is known to regulate functions of microRNAs (miRNA) during tumorigenesis [31,32]. We identi ed a region in miR-21-5p having a complementary binding sequence to PVT1, using Starbase 3.0 [33], and also generated a binding-de cient mutant of PVT1 (PVT1-mut) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

LncRNA PVT1 Mediated by ZFP36L2 Regulates Myocardial Ischemia/Reperfusion Injury and Attenuates Mitochondrial Fusion and Fission via Activating miR-21-5p/MARCH5 Axis

Huang¹,

Tan²,

Guo³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundAmong several leading cardiovascular disorders, ischemia-reperfusion (I/R) injury causes severe manifestations including acute heart failure, inflammation, and systemic dysfunction. Recently, there has been increasing evidence suggesting that alterations in mitochondrial morphology play a role in the prognoses of cardiac disorders. Long non-coding RNAs (lncRNAs) form major regulatory networks to modify gene transcription and translation. While several roles of lncRNAs have been explored in cancer and tumor biology, their implications on mitochondrial morphology and functions remain to be elucidated. MethodsThe functional roles of ZFP36L2 and lncRNA PVT1 were determined by a series of cardiomyocyte hypoxia/ reoxygenation (H/R) in vitro and myocardial I/R injury in vivo experiments. Quantitative Reverse transcription-polymerase chain reaction (qRT-PCR) and western blot analysis were used to detect the mRNA levels of ZFP36L2 and mitochondrial fission and fusion markers in the myocardial tissues and cardiomyocyte. Cardiac function was determined by immunohistochemistry, H&E, Masson’s staining and echocardiogram. Ultrastructural analysis of mitochondrial fission was performed using transmission electron microscopy (TEM). The mechanistic model of PVT1 with ZFP36L2 and miR-21-5p with MARCH5 was detected by subcellular fraction, RNA pull down, FISH, and luciferase reporter assays.ResultsIn this study, we report a novel regulatory axis involving lncRNA PVT1, microRNA miR-21-5p, and E3 ubiquitin ligase MARCH5, which alters mitochondrial morphology during myocardial I/R injury. Using an in vivo I/R injury mouse model and in vitro cardiomyocyte H/R model, we observed that zinc finger protein ZFP36L2 directly associated with PVT1 and altered mitochondrial fission and fusion. PVT1 also interacted with miR-21-5p and suppressed its expression and activity. Furthermore, we identified MARCH5 as a modifier of miR-21-5p, and expression of MARCH5 and its effect on mitochondrial fission and fusion were directly proportional to PVT1 expression during H/R injury. ConclusionsOur findings demonstrated that manipulation of PVT1-miR-21-5p-MARCH5-mediated mitochondrial fission and fusion via ZFP36L2 may be a novel therapeutic approach to regulate myocardial I/R injury.

show abstract

“…Altered lncRNA expression patterns for microsatellite-stable colorectal cancer indicated that several lncRNAs were continuously upregulated/downregulated during the adenoma-adenocarcinoma sequence [29] . Unlike previous studies that focused on one or more lncRNAs in CRC [30][31][32] , we rst conducted a systematic and comprehensive analysis using microarrays to reveal the differentially expressed pro les of lncRNAs and mRNAs in the malignant evolutionary process for pMMR CC. Thousands of dysregulated transcripts were identi ed in the ACS, including 5783 lncRNAs and 4483 mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Differentially Expressed Long Non-Coding RNA-mRNA in The Adenoma–Carcinoma Sequence of DNA Mismatch Repair Proficient Colon Cancer

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background DNA mismatch repair proficient colon cancer (pMMR CC) is the most common subtype of sporadic CC. However, the role of long non-coding RNAs (lncRNAs) in pMMR CC carcinogenesis has not been fully elucidated. Methods In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and Co-Expression Network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. Results A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values than serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. Conclusions Several lncRNAs play various roles in the adenoma–carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.

show abstract

lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis

Cited by 79 publications

References 58 publications

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

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

LncRNA PVT1 Mediated by ZFP36L2 Regulates Myocardial Ischemia/Reperfusion Injury and Attenuates Mitochondrial Fusion and Fission via Activating miR-21-5p/MARCH5 Axis

Comprehensive Analysis of Differentially Expressed Long Non-Coding RNA-mRNA in The Adenoma–Carcinoma Sequence of DNA Mismatch Repair Proficient Colon Cancer

Contact Info

Product

Resources

About