Roles of Long Noncoding RNAs in Regulating Epithelial-Mesenchymal Transition Process in Gastric Cancer

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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Roles of E-cadherin and Noncoding RNAs in the Epithelial–mesenchymal Transition and Progression in Gastric Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20122870 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2870 ◽

Cited By ~ 11

Author(s):

Irina V. Bure ◽

Marina V. Nemtsova ◽

Dmitry V. Zaletaev

Keyword(s):

Gastric Cancer ◽

Cancer Cell ◽

Rho Gtpase ◽

Epithelial Mesenchymal Transition ◽

Metastatic Cancer ◽

Noncoding Rnas ◽

Oncogenic Signaling ◽

Control Of Gene Expression ◽

Mesenchymal Transition ◽

E Cadherin

The epithelial–mesenchymal transition (EMT) is thought to be at the root of invasive and metastatic cancer cell spreading. E-cadherin is an important player in this process, which forms the structures that establish and maintain cell–cell interactions. A partial or complete loss of E-cadherin expression in the EMT is presumably mediated by mechanisms that block the expression of E-cadherin regulators and involve the E-cadherin-associated transcription factors. The protein is involved in several oncogenic signaling pathways, such as the Wnt/β-catenin, Rho GTPase, and EGF/EGFR, whereby it plays a role in many tumors, including gastric cancer. Such noncoding transcripts as microRNAs and long noncoding RNAs—critical components of epigenetic control of gene expression in carcinogenesis—contribute to regulation of the E-cadherin function by acting directly or through numerous factors controlling transcription of its gene, and thus affecting not only cancer cell proliferation and metastasis, but also the EMT. This review focuses on the role of E-cadherin and the non-coding RNAs-mediated mechanisms of its expressional control in the EMT during stomach carcinogenesis.

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Long noncoding RNAs AC026904 .1 is essential for TGF ‐β‐induced migration and epithelial‐mesenchymal transition through functioning as an enhancer of Slug in lung cancer cells

Environmental Toxicology ◽

10.1002/tox.22930 ◽

2020 ◽

Vol 35 (9) ◽

pp. 942-951

Author(s):

Jie Yao ◽

Xiaochen Lu ◽

Yuxuan Wang ◽

Jiaxi Li ◽

Bin Ni

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Lung Cancer Cells ◽

Mesenchymal Transition

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lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer

Molecular Medicine Reports ◽

10.3892/mmr.2020.11724 ◽

2020 ◽

Vol 23 (1) ◽

Author(s):

Shimei Wang ◽

Wei Zhu ◽

Ji Qiu ◽

Fei Chen

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Mesenchymal Transition

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The m6A reader IGF2BP3 Facilitates Gastric Cancer Progression Through Activating EMT via Upregulating MYC mRNA Stability

10.21203/rs.3.rs-1095901/v1 ◽

2021 ◽

Author(s):

Yiyi Ren ◽

Dandan Du ◽

Tong Liu ◽

Chuntao Wang ◽

Qinyu Yan ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Mrna Stability ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Cell Counting ◽

Gastric Cancer Cells ◽

Mesenchymal Transition ◽

Early Diagnose ◽

Cell Phenotypes

Abstract Background: N6-methyladenosine (m6A) RNA methylation plays an important biological role in cancer progression. Even so, the role of m6A modification in gastric cancer (GC) still needs further research. Methods: Firstly, based on the bioinformatics databases and human GC tissues analysis. Secondly, the IGF2BP3 expression in GC cells was measured by the quantificational real-time polymerase chain reaction and Western Blot. Then, the IGF2BP3 knockdown stable cells model was successfully constructed with the specific lentivirus-mediated short-hairpin RNA to explore the functions and mechanism of IGF2BP3 in GC. Next, the functions of IGF2BP3 on the cell phenotypes, including proliferation, invasion, migration, and Epithelial-mesenchymal transition process were clarified by the Cell Counting Kit-8, transwell, and WB experiments. Subsequently, RNA Immunoprecipitation analysis and mRNA stability experiments were used to verify the relationship between IGF2BP3 and MYC. Finally, in the rescue experiment, MYC was overexpressed and transfected into IGF2BP3 knockdown cells to further detect the influences on the cell phenotypes and the EMT process.Results: IGF2BP3 was up-regulated in GC. Meanwhile, IGF2BP3 had diagnostic and prognosis values for GC. Functionally, knockdown IGF2BP3 repressed gastric cancer cells proliferation, migration invasion and EMT process. Mechanically, IGF2BP3 activated the EMT process by improving the expression of MYC via combining with MYC mRNA and promoting its stability. Conclusions: Taken together, IGF2BP3 could activate the EMT process via increasing the MYC mRNA stability and expression to promote GC development, which provided insight into promising early diagnose and treatment for gastric cancer.

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Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.736929 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiaoying You ◽

Min Li ◽

Hongwei Cai ◽

Wenwen Zhang ◽

Ye Hong ◽

...

Keyword(s):

Gastric Cancer ◽

Calcium Binding ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Binding Protein ◽

Transition Process ◽

Calcium Binding Protein ◽

Mesenchymal Transition

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system, listed as the second cause of cancer-related deaths worldwide. S100 Calcium Binding Protein A16 (S100A16) is an acidic calcium-binding protein associated with several types of tumor progression. However, the function of S100A16 in GC is still not very clear. In this study, we analyzed S100A16 expression with the GEPIA database and the UALCAN cancer database. Meanwhile, 100 clinical GC samples were used for the evaluation of its role in the prognostic analysis. We found that S100A16 is significantly upregulated in GC tissues and closely correlated with poor prognosis in GC patients. Functional studies reveal that S100A16 overexpression triggers GC cell proliferation and migration both in vivo and in vitro; by contrast, S100A16 knockdown restricts the speed of GC cell growth and mobility. Proteomic analysis results reveal a large S100A16 interactome, which includes ZO-2 (Zonula Occludens-2), a master regulator of cell-to-cell tight junctions. Mechanistic assay results indicate that excessive S100A16 instigates GC cell invasion, migration, and epithelial-mesenchymal transition (EMT) via ZO-2 inhibition, which arose from S100A16-mediated ZO-2 ubiquitination and degradation. Our results not only reveal that S100A16 is a promising candidate biomarker in GC early diagnosis and prediction of metastasis, but also establish the therapeutic importance of targeting S100A16 to prevent ZO-2 loss and suppress GC metastasis and progression.

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