scholarly journals Long Noncoding RNA HOTAIR Promotes Epithelial-Mesenchymal Transition and Is a Suitable Target to Inhibit Peritoneal Dissemination in Human Scirrhous Gastric Cancers

Pathobiology ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 277-290
Author(s):  
Yoshifumi Takei ◽  
Toshifumi Hara ◽  
Akiko Suzuki ◽  
Keichiro Mihara ◽  
Kazuyoshi Yanagihara
Keyword(s):  
Gastric Cancer ◽  
Cell Line ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Peritoneal Dissemination ◽  
Luciferase Assay ◽  
Scirrhous Gastric Cancer ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Original Cell

<b><i>Objectives:</i></b> Scirrhous gastric cancer, which accounts for approximately 10% of all gastric cancers, often disseminates to the peritoneum, leading to intractable cases with poor prognosis. There is an urgent need for new treatment approaches for this difficult cancer. <b><i>Methods:</i></b> We previously established an original cell line, HSC-60, from a scirrhous gastric cancer patient and isolated a peritoneal-metastatic cell line, 60As6, in nude mice following orthotopic inoculations. In the present study, we focused on the expression of long noncoding ribonucleic acid (RNA) (lncRNA) in the cell lines and investigated the mechanism on peritoneal dissemination. <b><i>Results:</i></b> We demonstrated that an lncRNA, HOX transcript antisense RNA (HOTAIR), is expressed significantly more highly in 60As6 than HSC-60 cells. Then, using both HOTAIR knockdown and overexpression experiments, we showed that high-level expression of HOTAIR promotes epithelial-mesenchymal transition (EMT) in 60As6 cells. By luciferase assay, we found that HOTAIR directly targets and binds to miR-217, and that miR-217 directly binds to Zinc finger E-box-binding homeobox 1 (ZEB1). The knockdown of HOTAIR in 60As6 cells significantly reduced the invasion activity and peritoneal dissemination – and significantly prolonged the survival – in the orthotopic tumor mouse model. <b><i>Conclusion:</i></b> An EMT-associated pathway (the HOTAIR-miR-217-ZEB1 axis) appears to inhibit peritoneal dissemination and could lead to a novel therapeutic strategy against scirrhous gastric cancer in humans.

scholarly journals MicroRNAs Associated with Epithelial-Mesenchymal Transition Can Be Targeted to Inhibit Peritoneal Dissemination of Human Scirrhous Gastric Cancers

Pathobiology ◽  
2018 ◽  
Vol 85 (4) ◽  
pp. 232-246 ◽  
Author(s):  
Yoshifumi Takei ◽  
Guodong Shen ◽  
Ayami Morita-Kondo ◽  
Toshifumi Hara ◽  
Keichiro Mihara ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Peritoneal Dissemination ◽  
Mesenchymal Transition ◽  
Gastric Cancers

scholarly journals Long Noncoding RNA NEAT1 Regulates TGF-β2-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through the miR-34a/Snail1 and miR-204/Zeb1 Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Ning Dong
Keyword(s):  
Epithelial Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Lens Epithelial Cells ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Anterior Subcapsular Cataract

The aim of this study was to explore whether the long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1)/miR-34a/Snail1 and NEAT1/miR-204/Zeb1 pathways are involved in epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). Primary human LECs (HLECs) were separated and cultured. Our results identified that TGF-β2 induces NEAT1 overexpression in a dose-dependent manner and a time-dependent manner. Additionally, TGF-β2 induced downregulation of E-cadherin and upregulation of fibronectin in primary HLECs through a NEAT1-dependent mechanism. Microarray analysis showed that NEAT1 overexpression inhibited the miR-34a and miR-204 levels in the LECs. The expression of miR-34a and miR-204 was decreased, and the levels of Snail1 and Zeb1 were elevated in human posterior capsule opacification- (PCO-) attached LECs and the LECs obtained from anterior subcapsular cataract (ASC) by quantitative RT-PCR (qRT-PCR). Mechanistic studies revealed that NEAT1 negatively regulates miR-34a or miR-204, and miR-34a or miR-204 directly targets Snail1 or Zeb1 by luciferase assay and RNA-binding protein immunoprecipitation assay, respectively. Overall, the NEAT1/miR-34a/Snail1 and NEAT1/miR-204/Zeb1 pathways are involved in TGF-β2-induced EMT of HLECs. In summary, TGF-β2 induces NEAT1 overexpression, which in turn suggests that NEAT1 acts as a ceRNA targeting Snail1 or Zeb1 by binding miR-34a or miR-204, and promotes the progression of EMT of LECs.

scholarly journals Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial-mesenchymal transition of gastric cancer

Aging ◽  
2016 ◽  
Vol 8 (9) ◽  
pp. 2023-2038 ◽  
Author(s):  
Hu Zhou ◽  
Fubing Wang ◽  
Hao Chen ◽  
Qian Tan ◽  
Shili Qiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Novel Gastric Cancer Stem Cell-Related Marker LINGO2 Is Associated with Cancer Cell Phenotype and Patient Outcome

2019 ◽  
Vol 20 (3) ◽  
pp. 555 ◽  
Author(s):  
Jung Jo ◽  
Soo Park ◽  
Semi Park ◽  
Hee Lee ◽  
Chanyang Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Motility ◽  
Epithelial Mesenchymal Transition ◽  
Cell Phenotype ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Extracellular Signal ◽  
Gastric Cancer Treatment

The expression of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) has been reported in Parkinson’s disease; however, its role in other diseases is unknown. Gastric cancer is the second leading cause of cancer death. Cancer stem cells (CSC) are a subpopulation of cancer cells that contribute to the initiation and invasion of cancer. We identified LINGO2 as a CSC-associated protein in gastric cancers both in vitro and in patient-derived tissues. We studied the effect of LINGO2 on cell motility, stemness, tumorigenicity, and angiogenic capacity using cells sorted based on LINGO2 expression and LINGO2-silenced cells. Tissue microarray analysis showed that LINGO2 expression was significantly elevated in advanced gastric cancers. The overall survival of patients expressing high LINGO2 was significantly shorter than that of patients with low LINGO2. Cells expressing high LINGO2 showed elevated cell motility, angiogenic capacity, and tumorigenicity, while LINGO2 silencing reversed these properties. Silencing LINGO2 reduced kinase B (AKT)/extracellular signal-regulated kinase (ERK)/ERK kinase (MEK) phosphorylation and decreased epithelial-mesenchymal transition (EMT)-associated markers—N-Cadherin and Vimentin and stemness-associated markers— POU class 5 homeobox 1 (OCT4) and Indian hedgehog (IHH), and markedly decreased the CD44+ population. These indicate the involvement of LINGO2 in gastric cancer initiation and progression by altering cell motility, stemness, and tumorigenicity, suggesting LINGO2 as a putative target for gastric cancer treatment.

scholarly journals CREB3 Transactivates lncRNA ZFAS1 to Promote Papillary Thyroid Carcinoma Metastasis by Modulating miR-373-3p/MMP3 Regulatory Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Gang Wang ◽  
Yuan Le ◽  
Liping Wei ◽  
Lian Cheng
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Binding Sites ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Transcriptional Level ◽  
Papillary Thyroid ◽  
Mesenchymal Transition

The incidence rate of thyroid carcinoma ranks ninth among human malignancies, and it accounts for the most frequent malignancy in endocrine-related tumors. This study aimed to investigate the role of long noncoding RNA (lncRNA) ZFAS1 in the metastasis of papillary thyroid carcinoma (PTC) and the potential molecular mechanisms. Both ZFAS1 and MMP3 were highly expressed in thyroid carcinoma and PTC cell, as measured by the q-PCR and TCGA database. In addition, ZFAS1 induced TPC-1 metastasis through inducing the epithelial–mesenchymal transition (EMT) process. Besides, ZFAS1 knockdown by siRNA induced miR-373-3p expression and reduced MMP3 expression, as quantified by q-PCR and Western blotting. According to the luciferase assay, both ZFAS1 and MMP3 were classified as the direct targets of miR-373-3p. However, MMP3 itself did not affect ZFAS1. Using the online prediction tool, CREB3 was predicted as the transcription factor (TF) of ZFAS1 that contained two binding sites on its promoter region, and CREB3 was positively correlated with ZFAS1 in thyroid carcinoma cohorts. Results from the dual-luciferase assay and ChIP-qPCR indicated that both the two binding sites were essential for the transcription of ZFAS1. In conclusion, CREB3 activated lncRNA ZFAS1 at the transcriptional level to promote PTC metastasis by modulating miR-373-3p/MMP3.

scholarly journals LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rong-Hang Hu ◽  
Zi-Teng Zhang ◽  
Hai-Xiang Wei ◽  
Lu Ning ◽  
Jiang-Shan Ai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Mesenchymal Transition

Abstract Background Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. Results ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. Conclusions ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.

Sign in / Sign up

Export Citation Format

Share Document