The emerging co-regulatory role of long noncoding RNAs in epithelial-mesenchymal transition and the Warburg effect in aggressive tumors

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

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

Cell Death Discovery ◽

10.1038/s41420-021-00665-z ◽

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.

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The regulatory role of long noncoding RNAs in cancer

Cancer Letters ◽

10.1016/j.canlet.2017.01.010 ◽

2017 ◽

Vol 391 ◽

pp. 12-19 ◽

Cited By ~ 45

Author(s):

Ying Tang ◽

Belamy B. Cheung ◽

Bernard Atmadibrata ◽

Glenn M. Marshall ◽

Marcel E. Dinger ◽

...

Keyword(s):

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Regulatory Role

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Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20081924 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1924 ◽

Cited By ~ 49

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.

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