scholarly journals Biological functions and clinical significance of long noncoding RNAs in bladder cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Zhang ◽  
Xianwu Chen ◽  
Juntao Lin ◽  
Xiaodong Jin
Keyword(s):  
Bladder Cancer ◽  
Clinical Significance ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Research Progress ◽  
High Morbidity ◽  
Biological Functions ◽  
Mesenchymal Transition

AbstractBladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.

scholarly journals Biological Roles and Clinical Significance of Exosome-Derived Noncoding RNAs in Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yonghua Tong ◽  
Xiao Liu ◽  
Ding Xia ◽  
Ejun Peng ◽  
Xiaoqi Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Noncoding Rnas ◽  
Extracellular Vesicle ◽  
Bioactive Molecules ◽  
Clinical Value ◽  
Bioactive Substances ◽  
Mesenchymal Transition

Bladder cancer (BCa) is a common heterogeneous urinary system tumor with high malignancy and limited advancement in treatment. Limited understanding of BCa has not contributed to any significant progress in diagnosis or treatment, exploring the mechanisms underlying BCa has become an urgent research focus. Exosomes, a type of extracellular vesicle (EV), have drawn substantial interest for their important roles in mediating intracellular communication. Exosomes shuttle numerous bioactive molecules, and noncoding RNAs (ncRNAs) are among the most numerous. ncRNAs including microRNA, long noncoding RNA, and circular RNA are sorted and packaged into exosomes selectively and transferred into recipient cells to regulate their function. Exosomal ncRNAs are associated with hallmarks of BCa, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, lymphangiogenesis, and chemotherapy resistance. Exosomal ncRNAs can also be detected in urine and serum, making them encouraging biomarkers for BCa diagnosis and prognosis. More importantly, exosomes exhibit excellent biocompatibility and potential for diversified applications. The delivery of bioactive substances and drugs into specific cells has become a promising approach for precision therapy for BCa patients. In addition, cancer vaccines have also received increasing attention. In this review, we summarize the current research on the regulatory roles of exosomal ncRNAs in BCa tumorigenesis and progression, as well as their potential clinical value in accelerating the diagnosis and therapy of BCa.

scholarly journals Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Noncoding Rna ◽  
Pancreatic Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

scholarly journals An epithelial–mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Hang Tong ◽  
Tinghao Li ◽  
Shun Gao ◽  
Hubin Yin ◽  
Honghao Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Functional Enrichment ◽  
Diagnostic Efficacy ◽  
Mesenchymal Transition

Abstract Bladder cancer is a common malignant tumour worldwide. Epithelial–mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

scholarly journals Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer

2019 ◽  
Vol 20 (8) ◽  
pp. 1924 ◽  
Author(s):  
Gugnoni ◽  
Ciarrocchi
Keyword(s):  
Cancer Biology ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Protein Localization ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Mesenchymal Transition ◽  
Multistep Process ◽  
Genomic Studies

Epithelial–mesenchymal transition (EMT) is a multistep process that allows epithelial cells to acquire mesenchymal properties. Fundamental in the early stages of embryonic development, this process is aberrantly activated in aggressive cancerous cells to gain motility and invasion capacity, thus promoting metastatic phenotypes. For this reason, EMT is a central topic in cancer research and its regulation by a plethora of mechanisms has been reported. Recently, genomic sequencing and functional genomic studies deepened our knowledge on the fundamental regulatory role of noncoding DNA. A large part of the genome is transcribed in an impressive number of noncoding RNAs. Among these, long noncoding RNAs (lncRNAs) have been reported to control several biological processes affecting gene expression at multiple levels from transcription to protein localization and stability. Up to now, more than 8000 lncRNAs were discovered as selectively expressed in cancer cells. Their elevated number and high expression specificity candidate these molecules as a valuable source of biomarkers and potential therapeutic targets. Rising evidence currently highlights a relevant function of lncRNAs on EMT regulation defining a new layer of involvement of these molecules in cancer biology. In this review we aim to summarize the findings on the role of lncRNAs on EMT regulation and to discuss their prospective potential value as biomarkers and therapeutic targets in cancer.

scholarly journals A positive feedback loop between TAZ and miR-942-3p modulates proliferation, migration, epithelial-mesenchymal transition process and glycometabolism in human bladder cancer

2020 ◽  
Author(s):  
Feifan Wang ◽  
Mengjing Fan ◽  
Xuejian Zhou ◽  
Yanlan Yu ◽  
Yueshu Cai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Feedback Loop ◽  
Epithelial Mesenchymal Transition ◽  
Biological Functions ◽  
Positive Feedback Loop ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Bladder Cancer Cells

Abstract Background: Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to involve in tumor progression, epithelial-mesenchymal transition (EMT) process and glycometabolism modulation. Herein, the underlying molecular mechanisms of TAZ-induced biological effects in bladder cancer were discovered; Methods: qRT-PCR, western blot and immunohistochemistry were performed to determine the level of TAZ in bladder cancer cells and tissues; CCK-8 assay, Colony formation assay, wound healing assay and Transwell assay were performed to evaluate the functions of TAZ, miR-942-3p and GAS1. qRT-PCR and western blot were used to determine the expression levels of related genes. Chromatin immunoprecipitation and dual-luciferase reporter assay confirmed the interaction between TAZ and miR-942. In vivo tumorigenesis assay and colorimetric assay of glycolysis were also conducted; Results: We determined the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the suppression of cell proliferation, EMT process and glycolysis induced by TAZ knockdown. Further, miR-942-3p resulted in restrained expression of growth arrest-specific 1 (GAS1) to modulate biological functions; Conclusion: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression, and illustrated that TAZ and miR-942-3p might be potential therapeutic targets for bladder cancer treatment.

scholarly journals PBX1 Participated in Estrogen Mediated Bladder Cancer Progression and Chemo-Resistance through Affecting Estrogen Receptors

2021 ◽  
Author(s):  
Yang Zhao ◽  
Jizhong Che ◽  
Aimin Tian ◽  
Gang Zhang ◽  
Yankai Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Estrogen Receptors ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
High Morbidity ◽  
Promoting Effect ◽  
Mesenchymal Transition ◽  
Survival Status ◽  
Underlying Mechanisms ◽  
Muscle Invasive

Abstract Bladder cancer (BCa) is a common cancer associated with high morbidity and mortality worldwide. Pre-B-cell leukemia transcription factor 1 (PBX1) has been reported to be involved in tumor progression. The aim of the study was to explore the specific role of PBX1 in BCa and its underlying mechanisms. The relative expressions of PBX1 in muscle-invasive BCa tissues and cell lines were analyzed through RT-qPCR and Western blotting. Kaplan–Meier analysis was used to analyze the relationship between PBX1 levels and survival status. Co-immunoprecipitation (CO-IP) and chromatin immunoprecipitation (ChIP)-qPCR assay were adopted to verify the interaction between PBX1 and Estrogen receptors (ERs), and explore the ER-dependent genes transcription. The results shown that PBX1 was upregulated in invasive BCa patients and BCa cells, positively associated with tumor size, lymph node metastasis, distant metastasis and poorer survival status. Overexpression of PBX1 promoted cell growth, invasion, epithelial-mesenchymal transition (EMT) process and cisplatin resistance in BCa cells, while the silence of PBX1 showed opposite effects. Further, PBX1 interacted with Estrogen receptors (ERs) and was required for the ER function. Overexpression of PBX1 aggravated the tumor-promoting effect of estrogen on BCa cells, while partially suppressed the inhibitory effects of ER antagonist AZD9496 on BCa cells. In summary, this study revealed that PBX1 participated in estrogen mediated BCa progression and chemo-resistance through binding and activating estrogen receptors. Hence, PBX1 may serve as a potential prognostic and therapeutic target for BCa treatment.

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