scholarly journals The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengpeng Zhao ◽  
Xiaoling Ling ◽  
Yunxia Xia ◽  
Bingxue Yan ◽  
Quanlin Guan
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Rna Immunoprecipitation ◽  
Functional Relevance ◽  
And Migration

Abstract Background Previous studies have revealed the key functions of N6-methyladenosine (m6A) modification in breast cancer (BC). MALAT1 as a highly m6A modified lncRNA associated with cancer development and metastasis, but the functional relevance of m6A methyltransferase and MALAT1 in BC is still unknown. Here, our study investigated the effects of the novel m6A methyltransferase METTL3 on epithelial-mesenchymal transition (EMT) in BC via the MALAT1/miR-26b/HMGA2 axis. Methods Firstly, we collected clinical BC samples and cultured BC cells, and detected mRNA and protein levels in the human samples and human cell lines by RT-qPCR and Western blot, respectively. Then, the binding of MALAT1 and miR-26b and the targeting relationship between miR-26b and HMGA2 were examined by dual-luciferase assay. Moreover, the binding of MALAT1 and miR-26b was tested by RNA pull down and RNA immunoprecipitation (RIP) assays. Methylated-RNA immunoprecipitation (Me-RIP) was used to detect the m6A modification level of MALAT1. The interaction of METTL3 and MALAT1 was detected by photoactivatable ribonucleoside-crosslinking immunoprecipitation (PAR-CLIP). Finally, effects on invasion and migration were detected by Transwell. Results In BC, the level of miR-26b was consistently low, while the levels of METTL3, MALAT1 and HMGA2 were high. Further experiments showed that METTL3 up-regulated MALAT1 expression by modulating the m6A modification of MALAT1, and that MALAT1 could promote the expression of HMGA2 by sponging miR-26b. In BC cells, we found that silencing METTL3 could inhibit EMT and tumor cell invasion by suppressing MALAT1. Furthermore, MALAT1 mediated miR-26b to target HMGA2 and promote EMT, migration, and invasion. In summary, METTL3 promoted tumorigenesis of BC via the MALAT1/miR-26b/HMGA2 axis. Conclusions Silencing METTL3 down-regulate MALAT1 and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.

MiR-21 Promotes the Invasion and Metastasis of Gastric Cancer Cells by Activating Epithelial-Mesenchymal Transition

2019 ◽  
Vol 60 (5-6) ◽  
pp. 208-218 ◽  
Author(s):  
Tao Xiao ◽  
Zhigang Jie
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: Gastric cancer (GC) is one of the most common malignant tumors. It is likely to occur in lymph nodes and is prone to distant metastasis in its early stages, which portends a poor prognosis. Previous studies have shown that miRNA-21 was abnormally highly expressed and associated with early metastasis in GC, but the mechanism by which it regulates the invasion and metastasis of GC has not been elucidated. Methods: Epithelial-mesenchymal transition (EMT) is an important pathologic basis of tumor invasion and metastasis, and in this study, the relationship between miRNA-21 and EMT in GC invasion and metastasis was investigated using RT-qPCR, Western blot, and wound scratch and transwell assays. Results: We found that miRNA-21 expression in GC cell lines was higher than in a gastric mucosal epithelial cell line. After transfection with an miRNA-21 mimic, the upregulation of EMT was found to promote migration and invasion of MGC-803 cells. However, the downregulation of EMT was found to accompany the inhibition of invasion and migration of GC cells after downregulation of miRNA-21 expression due to the transfection of an miRNA-21 inhibitor. Conclusions: These findings suggest that miRNA-21 might promote the invasion and metastasis of GC by upregulating EMT.

Interleukin-27 Inhibits Trophoblast Cell Invasion and Migration by Affecting the Epithelial–Mesenchymal Transition in Preeclampsia

2018 ◽  
Vol 26 (7) ◽  
pp. 928-938 ◽  
Author(s):  
Huisheng Ge ◽  
Nanlin Yin ◽  
Ting-Li Han ◽  
Dongni Huang ◽  
Xuehai Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Signal Transducer ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Epithelial Phenotype ◽  
And Migration

Preeclampsia (PE) is a pregnancy-specific disorder representing a major cause of maternal and perinatal morbidity and mortality. Invasive and migratory phenotypes are acquired by trophoblasts through the process of epithelial–mesenchymal transition (EMT). Studies have shown that trophoblast EMT events are dysregulated in PE and play an important role in its development. Dysregulation of interleukin (IL)-27 and IL-27R (T-cell cytokine receptor (TCCR)/WSX -1) is relevant to PE. In this study, our results demonstrated that IL-27 did not significantly affect the proliferation and apoptosis of HTR -8/SVneo trophoblast cells, while it did significantly inhibit trophoblast invasion and migration. The expression of EMT-related proteins in HTR-8/SVneo cells and extravillous explants was detected after treatment with IL-27. Expression of epithelial markers was increased, and mesenchymal marker expression was reduced. Furthermore, we found that IL-27 could induce significant phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and Signal Transducer and Activator of Transcription 3 (STAT3) in a time-dependent manner in HTR-8/SVneo cells. Selective inhibitors of STAT1 (STAT1 siRNA) and STAT3 (STAT3 siRNA) were used to determine whether both STAT1 and STAT3 are required for IL-27-mediated inhibition of EMT. STAT1 inhibition in IL-27-treated cells attenuated the IL-27 effect, while the inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. These results demonstrate that IL-27 may inhibit trophoblast cell migration and invasion by affecting the EMT process through an STAT1-dominant pathway in PE.

miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway

2021 ◽  
Vol 21 ◽  
Author(s):  
Chen-hui Bao ◽  
Lin Guo
Keyword(s):  
Gastric Cancer ◽  
Target Gene ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Mirna Sequence ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
The Hippo Pathway

Background: Gastric cancer (GC) accounts for high mortality, which seriously threatens people’s health. This study set out to probe into the effect and mechanism of miR-27b-3p on invasion and migration of GC. Methods: The miRNA sequence data of GC was acquired from The Cancer Genome Atlas (TCGA) database. The differential expression of miRNAs (DEMis) was acquired through R packages “edgeR” and “limma.” TargetScan, picTar, RNA22, PITA, and miRanda were performed to predict the target gene of miR-27b-3p. Western-blot and RT-PCR were applied to detect the expression level of the selected candidate. Transwell assays evaluated the effect of miR-27b-3p and runt-related transcription factor 1 (RUNX1) on cell migration and invasion. The rescue assay was achieved by co-culture with mimics of miR-27b-3p and vector of RUNX1. The psiCHECK2 vector was used in the luciferase report assay. Results: We found miR-27b-3p was down-regulated in GC and associated with GC patients' poor survival based on the TCGA data and bioinformatics analysis. Furthermore, RUNX1 was the target gene of miR-27b-3p, which was proved by the luciferase report assay. miR-27b-3p and RUNX1 jointly participate in the regulation of the Hippo pathway. The up-regulated miR-27b-3p could inhibit epithelial–mesenchymal transition (EMT) as well as invasion and migration. However, an overexpressed RUNX1 could weaken this phenomenon. Conclusion: miR-27b-3p was down-regulated in GC, and it could regulate the Hippo pathway and affect EMT by inhibiting RUNX1 expression.

scholarly journals Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

2017 ◽  
Vol 42 (5) ◽  
pp. 1847-1856 ◽  
Author(s):  
Zhi-Dong Lv ◽  
Hai-Bo Wang ◽  
Xiang-Ping Liu ◽  
Li-Ying Jin ◽  
Ruo-Wu Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Association Studies ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Node Metastasis ◽  
And Migration

Background/Aims: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. Methods: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/β-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. Results: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of β-catenin, inhibited wnt/β-catenin signaling pathway. Conclusion: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

Expression of lncRNA TINCR in the placenta of patients with pre-eclampsia and its effect on the biological behaviours of trophoblasts

Zygote ◽  
2021 ◽  
pp. 1-9
Author(s):  
Li Qin ◽  
Qin Yang ◽  
Zhiyi Fei ◽  
Dandan Zhang
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Terminal Differentiation ◽  
S Phase ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
Related Proteins

Summary To explore the effect of lncRNA TINCR on the biological behaviours of trophoblasts, we detected and analyzed the expression of terminal differentiation-induced non-protein coding RNA (TINCR) in the placenta tissues of pre-eclamptic and non-pre-eclamptic pregnant women. The gain- and loss-of-function of TINCR was performed to examine the proliferation, migration and invasion abilities of Htr-8/Svneo cells. The levels of epithelial–mesenchymal transition (EMT)-related proteins, cyclin and Wnt/β-catenin pathway were detected. High expression of lncRNA TINCR appeared in placental tissues of patients with pre-eclampsia. The proliferation, invasion and migration of Htr-8/Svneo cells were promoted by TINCR downregulation; the cells were transited from G0/G1 to S phase; and EMT was promoted and the Wnt/β-catenin pathway was activated. In summary, the downregulation of lncRNA TINCR activated the Wnt/β-catenin pathway and promoted the proliferation, invasion and migration of Htr-8/Svneo cells. This study may provide a theoretical basis for treatment of patients with pre-eclampsia.

scholarly journals MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/β-cadherin pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qian Xu ◽  
Qianqian Zhang ◽  
Mengli Dong ◽  
Yuan Yu
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Homeobox Protein ◽  
Cancer Tissues

Abstract Background Previous studies had shown that microRNA-638 (miR-638) exhibited different effects in malignant tumors. Moreover, the function of miR-638 has not been reported in breast cancer. Hence, we designed this research to explore the function of miR-638 in breast cancer. Methods Firstly, miR-638 expressions were measured in breast cancer tissues via RT-qPCR. Protein expressions were detected through immunocytochemical (IHC) assay and western blot analysis. Then, Cell Counting Kit-8 (CCK-8) assay and Transwell assay were conducted to observe proliferation and motility of the cells. Dual luciferase assay was performed to confirm the binding site between miR-638 and Homeobox protein Hox-A9 (HOXA9). Results Reduced expression of miR-638 was detected in breast cancer. And low miR-638 expression was related to poor prognosis in patients with breast cancer. Functionally, the viability, migration, and invasion of the breast cancer cells were suppressed by miR-638 overexpression. Furthermore, miR-638 can directly bind to HOXA9, and increased expression of HOXA9 was also detected in breast cancer. In particular, HOXA9 upregulation can impair anti-tumor effect of miR-638 in breast cancer, and miR-638 can hinder the Wnt/β-cadherin pathway and epithelial-mesenchymal transition (EMT) in breast cancer. Conclusion miR-638 inhibits breast cancer progression through binding to HOXA9.

scholarly journals LncRNA SNHG3 Promotes Gastric Cancer Cells Proliferation, Migration, and Invasion by Targeting miR-326

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jun Rao ◽  
Jinjin Fu ◽  
Chuchen Meng ◽  
Jin Huang ◽  
Xiangrong Qin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Rna Immunoprecipitation ◽  
And Migration

The function and possible mechanism of lncRNA Small Nucleolar RNA Host Gene 3 (SNHG3) in GC have not been fully studied. The aim of our study was to investigate the role of SNHG3 in the proliferation, migration, and invasion of GC cell lines. The expressions of SNHG3, miR-326, and TWIST in GC9811-P GC cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein levels of TWIST and EMT-related genes. Luciferase reporter gene analysis and RNA immunoprecipitation (RIP) analysis confirmed the interaction between lncRNA SNHG3, miR-326, and TWIST. CCK-8 and Transwell assays were performed to detect cell proliferation, invasion, and migration abilities. The results showed that lncRNA SNHG3 and TWIST were highly expressed in GC cell lines, while miR-326 was expressed to a low degree. Moreover, lncRNA SNHG3 knockdown or miR-326 overexpression significantly inhibited cell proliferation, migration, and invasion of GC cell lines. In addition, TWIST overexpression can reverse the inhibition of lncRNA SNHG3 knockdown or miR-326 overexpression on cell proliferation, migration, and invasion. In conclusion, lncRNA SNHG3 may promote GC progression through the miR-326/TWIST axis, which may provide a new diagnostic and prognostic biomarker for GC.

Matrix Metalloproteinase (MMP)-12 Promote Invasion and Migration of Esophageal Squamous Cell Carcinoma Cell by Epithelial-Mesenchymal Transition

2019 ◽  
Vol 9 (8) ◽  
pp. 1120-1126
Author(s):  
Dong-Hui Shi ◽  
Jiang Jin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Matrix Metalloproteinase ◽  
Cell Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Over Expression ◽  
And Migration

The present study aimed to investigate the role of matrix metalloproteinase (MMP)-12 on cell migration and invasion of esophageal squamous cell carcinoma (ESCC) though epithelial-mesenchymal transition (EMT). The ESCC cell lines (ECA-109, KYSE-30, KYSE-410, KYSE-520) and normal esophageal epithelial cells (HEEC) were cultured. ECA-109 cells were then chosen to be transfected with the plasmids of MMP-12 over-expression, MMP-12 inhibitor, E-cad over-expression and empty control vectors. The protein and mRNA levels of MMP-12 were detected using western blot and qRT-PCR analysis. Transwell and wound healing assays were used to assess cell invasion and migration. Results indicated that MMP-12 was upregulated significantly in all the ESCC cell lines. Overexpression of MMP-12 increased MMP-12 expression, and the abilities of invasion and migration of ECA-109 cells. Overexpression of MMP-12 increased the expression of N-cad and vimentin, but decreased E-cad expression. Additionally, we found that cells treated with inhibitor-MMP-12 were opposite to the above results. Moreover, up-regulation of E-cad were eliminated all effects on ECA-109 cells caused by MMP-12 over-expression. In conclusion, MMP-12 promoted ECA-109 cells migration and invasion by the alteration of the EMT marker protein, which is one of its mechanisms. Therefore, MMP-12 may be a new therapeutic target for ESCC.

Sign in / Sign up

Export Citation Format

Share Document