scholarly journals POU2F1 Promotes Cell Viability and Tumor Growth in Gastric Cancer through Transcriptional Activation of lncRNA TTC3-AS1

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jixu Wang ◽  
Ke Xiao ◽  
Futao Hou ◽  
Lusheng Tang ◽  
Dan Luo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Transcriptional Activation ◽  
Function Analysis ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Pou Domain ◽  
New Perspective ◽  
Transcription Factor 1 ◽  
Normal Controls

POU domain, class 2, transcription factor 1 (POU2F1) is involved in the development of gastric cancer (GC). However, the molecular mechanism has not been fully elucidated. Here, we identified a novel lncRNA named TTC3-AS1 that was potentially regulated by POU2F1 and investigated their roles in GC progression. Bioinformatics analysis suggested that high expression of POU2F1 predicted poor prognosis in patients with GC. We further screened out an lncRNA TTC3-AS1 that may be transcriptionally activated by POU2F1 according to the JASPAR database, and POU2F1 and TTC3-AS1 were highly expressed in GC cells and tissues compared with normal controls (NCs). Function analysis revealed that both POU2F1 and TTC3-AS1 played oncogenic roles by promoting cell viability, migration, and invasion in GC. qRT-PCR analysis showed that POU2F1 improved the expression of TTC3-AS1 in GC cells, while TTC3-AS1 knockdown or overexpression had no effect on POU2F1 expression. The results of chromatin immunoprecipitation and DNA-affinity precipitation assays indicated that POU2F1 directly bound to the promoter region of TTC3-AS1 and activated its transcription. TTC3-AS1 knockdown neutralized the protumor effects of POU2F1 overexpression in GC cell lines as well as mouse models of GC, which suggested that TTC3-AS1 mediates the oncogenic function of POU2F1. In summary, POU2F1 promoted GC progression by transcriptionally activating TTC3-AS1; thus, this study provided a new perspective for the mechanism of GC progression.

Silencing of hsa_circ_0000515 Inhibits Proliferation, Migration and Invasion of Gastric Cancer Cells by Sponging miR-615-5p In Vitro

2021 ◽  
Vol 11 (8) ◽  
pp. 1466-1476
Author(s):  
Xuli Wang ◽  
Aiping Wang
Keyword(s):  
Gastric Cancer ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Gastric Cancer Cells ◽  
Novel Target

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.

LncRNA PCAT18/miR-301a/TP53INP1 axis is involved in gastric cancer cell viability, migration and invasion

2020 ◽  
Vol 168 (5) ◽  
pp. 547-555
Author(s):  
Jin Dou ◽  
Daoyuan Tu ◽  
Haijian Zhao ◽  
Xiaoyu Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cell Lines ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Cell Proliferation And Metastasis

Abstract MiR-301a is as an oncogene involved in the regulation of gastric cancer (GC) progression, but the underlying mechanism is unclear. This study was to explore the lncRNA PCAT18/miR-301a/TP53INP1 axis in regulating the GC cell proliferation and metastasis. In the present study, GC tissues and cell lines were collected for the detection of PCAT18 expression. Herein, we found that PCAT18 is significantly decreases in human GC tissues and five GC cell lines. Overexpression of PCAT18 inhibits cell viability, invasion and migration of GC cells and tumour growth of GC xenograft tumours. PCAT18 negatively regulates the expression level of miR-301a. The interaction between PCAT18 and miR-301a is confirmed by RIP and RNA pull down. MiR-301a mimic increases cell viability and promotes cell migration and invasion and reverses the inhibitory action of PCAT18. TP53INP1 expression is negatively regulated by miR-301a and TP53INP1/miR-301a is involved in GC viability, migration and invasion. The promoting of PCAT18 on TP53INP1 expression is abolished by miR-301a overexpression. In conclusion, lncRNA PCAT18 acts as a tumour suppressor for GC and lncRNA PCAT18, miR-301a and TP53INP1 comprise a signal axis in regulating GC cell proliferation, migration and invasion.

scholarly journals Transcriptome Analysis of the Inhibitory Effect of Astaxanthin on Helicobacter pylori-Induced Gastric Carcinoma Cell Motility

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 365 ◽  
Author(s):  
Suhn Hyung Kim ◽  
Hyeyoung Kim
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Cell Motility ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Human Gastric Cancer ◽  
Gastric Carcinoma Cell ◽  
H Pylori

Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism of action of ASTX in H. pylori-infected gastric epithelial cells is not well understood. To gain insight into this process, we carried out a comparative RNA sequencing (RNA-Seq) analysis of human gastric cancer AGS (adenocarcinoma gastric) cells as a function of H. pylori infection and ASTX administration. The results were used to identify genes that are differently expressed in response to H. pylori and ASTX. Gene ontology (GO) analysis identified differentially expressed genes (DEGs) to be associated with cell cytoskeleton remodeling, motility, and/or migration. Among the 20 genes identified, those encoding c-MET, PI3KC2, PLCγ1, Cdc42, and ROCK1 were selected for verification by real-time PCR analysis. The verified genes were mapped, using signaling networks contained in the KEGG database, to create a signaling pathway through which ASTX might mitigate the effects of H. pylori-infection. We propose that H. pylori-induced upregulation of the upstream regulator c-MET, and hence, its downstream targets Cdc42 and ROCK1, is suppressed by ASTX. ASTX is also suggested to counteract H. pylori-induced activation of PI3K and PLCγ. In conclusion, ASTX can suppress H. pylori-induced gastric cancer progression by inhibiting cytoskeleton reorganization and reducing cell motility through downregulation of c-MET, EGFR, PI3KC2, PLCγ1, Cdc42, and ROCK1.

scholarly journals Genome-wide identification of ZF-HD gene family in Triticum aestivum: Molecular evolution mechanism and function analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256579
Author(s):  
Hongli Niu ◽  
Pengliang Xia ◽  
Yifeng Hu ◽  
Chuang Zhan ◽  
Yiting Li ◽  
...  
Keyword(s):  
Gene Family ◽  
Function Analysis ◽  
Expression Patterns ◽  
Pcr Analysis ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Wheat Evolution ◽  
New Perspective ◽  
Almost All ◽  
And Function

ZF-HD family genes play important roles in plant growth and development. Studies about the whole genome analysis of ZF-HD gene family have been reported in some plant species. In this study, the whole genome identification and expression profile of the ZF-HD gene family were analyzed for the first time in wheat. A total of 37 TaZF-HD genes were identified and divided into TaMIF and TaZHD subfamilies according to the conserved domain. The phylogeny tree of the TaZF-HD proteins was further divided into six groups based on the phylogenetic relationship. The 37 TaZF-HDs were distributed on 18 of 21 chromosomes, and almost all the genes had no introns. Gene duplication and Ka/Ks analysis showed that the gene family may have experienced powerful purification selection pressure during wheat evolution. The qRT-PCR analysis showed that TaZF-HD genes had significant expression patterns in different biotic stress and abiotic stress. Through subcellular localization experiments, we found that TaZHD6-3B was located in the nucleus, while TaMIF4-5D was located in the cell membrane and nucleus. Our research contributes to a comprehensive understanding of the TaZF-HD family, provides a new perspective for further research on the biological functions of TaZF-HD genes in wheat.

scholarly journals Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jiawei Lu ◽  
Ying Xu ◽  
Wenjie Xie ◽  
Yinbing Tang ◽  
Heteng Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcriptional Activation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Promoter Regions ◽  
Systematic Analysis ◽  
Downstream Target ◽  
Signaling Axis ◽  
Wnt1 Expression

AbstractThe long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/β-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/β-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/β-catenin signaling could effectively abolish the activation of Wnt/β-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/β-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.

Inhibition of migration and invasion of gastric cancer cells by Snail-regulated MiR-375 through JAK2 targeting.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 56-56
Author(s):  
Xu Yanjun ◽  
Zhou Tianhua ◽  
Si Jianmin ◽  
Zhuo Wei
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Expression Level ◽  
Luciferase Assay ◽  
Surrounding Tissue ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells

56 Background: Migration and invasion of cancer cells are essential process during cancer metastatic procession. In gastric cancer, cells invasion into the surrounding tissue is a crucial early step. However, the mechanisms have not been fully understood. MicroRNAs, which are a class of small single-stranded non-coding RNA, participate in the malignant progressions of cancer, including metastasis. We study the association between specific dysregulated miRNA and specific metastasis step of gastric cancer, which will provide insights into the potential mechanisms of gastric cancer cells migration, invasion and metastasis. Methods: The expression of miR-375 was assayed using the quantitative real-time PCR analysis. Scratch-wound healing assay, Transwell migration and invasion assay were conducted to study the migration and invasion abilities of cells. Animal experiment was also conducted to examine the effect on liver and lung metastases by overexpression of miR-375. Luciferase assay was conducted to study the association between Snail and miR-375. Results: MiR-375 is downregulated in gastric cancer cells with greater migration and invasion abilities. The expression level of miR-375 is decreased in gastric cancer tissues from metastasis-positive patients compared with that from metastasis-free patients. Overexpression of miR-375 inhibits the migration and invasion abilities of gastric cancer cells. JAK2, which may be a target gene of miR-375, could reverses miR-375 induced inhibition of gastric cancer cells migration and invasion. Liver metastasis was not detected in mice injected with miR-375 overexpressed cells but was apparent in mice injected with cells which were transfected with control vector. The transcription factor Snail, which binds directly to the putative promoter of miR-375, could reduce the expression level of miR-375 significantly. A distinct inverse correlation was found between miR-375 expression and Snail mRNA level. Conclusions: These findings demonstrate that tumor suppressor miR-375, whose expression is directly regulated by the transcription factor Snail, inhibits gastric cancer cells migration, invasion and metastasis by targeting an important protein JAK2.

scholarly journals miR-96-5p enhances cell proliferation and invasion via targeted regulation of ZDHHC5 in gastric cancer

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Baolong Wang ◽  
Xianrong Liu ◽  
Xiangtao Meng
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Target Gene ◽  
Caspase 3 ◽  
Migration And Invasion ◽  
Caspase 9 ◽  
Receptor Assay ◽  
Direct Target Gene ◽  
Cox 2

Abstract Objective: To explore the biological function and mechanism of miR-96-5p in gastric cancer. Methods: The expression of differently expressed microRNAs (DEMs) related to gastric adenocarcinoma (GAC) prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR. A target gene miR-96-5p was selected using TargetScan, miRTarBase, miRDB databases. The combination of miR-96-5p and ZDHHC5 was verified by luciferase receptor assay. To further study the function and mechanism of miR-96-5p, we treated MGC-803 cells with miR-96-5p inhibitor and si-ZDHHC5, then detected cell viability, apoptosis, migration and invasion ability, as well as the expression of ZDHHC5, Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, and COX-2 by Western blot. Results: Compared with adjacent normal samples, the levels of miR-96-5p, miR-222-5p, and miR-652-5p were remarkably increased, while miR-125-5p, miR-145-3p, and miR-379-3p were significantly reduced in GAC tumor samples (P<0.01), which were consistent with bioinformatics analysis. Furthermore, ZDHHC5 was defined as a direct target gene of miR-96-5p. miR-96-5p silence significantly reduced cell viability, increased cell apoptosis, and suppressed cell migration and invasion, as well as inhibited the expression of Bcl-2 and COX-2 and promoted Bax, cleaved caspase-3 and cleaved caspase-9 level in MGC-803 cells (P<0.01). Notably, ZDHHC5 silence reversed the inhibiting effects of miR-96-5p on MGC-803 cells growth and metastasis Conclusion: Our findings identified six microRNAs (miRNAs; miR-96-5p, miR-222-5p, miR-652-5p, miR-125-5p, miR-145-3p, and miR-379-3p) related to GAC prognosis, and suggested that down-regulated miR-96-5p might inhibit tumor cell growth and metastasis via increasing ZDHHC5 expression enhance MGC-803 cell apoptosis, as well as decrease MGC-803 cell metastasis.

MicroRNA-760 inhibits cell viability and migration through down-regulating BST2 in gastric cancer

2020 ◽  
Vol 168 (2) ◽  
pp. 159-170
Author(s):  
Weiyu Liu ◽  
Yan Li ◽  
Shuting Feng ◽  
Yadi Guan ◽  
Yong Cao
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Primary Tumour ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mouse Xenograft Model ◽  
Cancer Tissues

Abstract Gastric cancer is one of the most common types of carcinoma with a threat to global health. MicroRNA-760 (miR-760) was significantly down-regulated in the primary tumour of patients with advanced gastric cancer. However, the role of miR-760 in gastric cancer is still unclear. Herein, miR-760 was down-regulated in gastric cancer tissues. Moreover, miR-760 overexpression and knockdown were conducted in gastric cancer cells (MGC-803 and SGC-7901) in vitro. The in vitro functional assays proved that miR-760 overexpression reduced cell viability, cell cycle, migration and invasion, promoted apoptosis and suppressed MMP activity in MGC-803 cells. Conversely, miR-760 knockdown led to the opposite in SGC-7901 cells. Notably, bone marrow stromal antigen 2 (BST2) was verified as a target gene of miR-760. MiR-760 mimics down-regulated BST2 level in gastric cancer tissues and in MGC-803 cells, whereas miR-760 inhibitor up-regulated its level in SGC-7901 cells. MiR-760-regulated cell properties through reduction of BST2. In addition, miR-760 inhibited tumourigenesis in a nude mouse xenograft model in vivo. In conclusion, our results demonstrated that miR-760 exhibited a suppressive role in gastric cancer via inhibiting BST2, indicating that miR-760/BST2 axis may provide promising therapeutic target for gastric cancer.

scholarly journals miR-1273h-5p Suppresses the Penetration and Pervasion of Gastric Cancer Cells via Suppressing CXCL12 Expression

2021 ◽  
Author(s):  
Yi-Chen Wang ◽  
Song Lu ◽  
Xiao-Jiang Zhou ◽  
Li Yang ◽  
ping liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Biological Function ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Gastric Cancer Cells ◽  
Cxcl12 Expression ◽  
Tissue Samples ◽  
Normal Tissues

Abstract Purpose: microRNAs (miRNAs), which may function as oncogenes or tumor suppressors, have been verified in the development of breast carcinoma, melanoma, and some other tumors. The dysregulated miR-1273h-5p in tissue samples of gastric cancer (GC) may be involved in the progression of GC. The aim of this study was to verify the biological function of miR-1273h-5p in GC progression.Method: The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected by microarrays, and polymerase chain reaction (PCR) analysis was used for miR-1273h-5p and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA expressions. The effect of miR-1273h-5p on cell proliferation and apoptosis was evaluated by CCK-8 assay and flow cytometry; cell migration and invasion were observed by using the transwell method. In addition, protein levels were determined by Western blot. SGC-7901 cell transfected gene sequences were injected into BALB/c-nu mice to establish a xenograft model in order to validate the biological function of miR-1273h-5p in vivo.Results: Compared to tumor-adjacent normal tissue and GES-1 cells, miR-1273h-5p was significantly down-regulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant up-regulation of CXCL12 was observed when the miR-1273h-5p was down-regulated in GC cells. Additionally, tumor tissues were collected from mice after 21 days of feeding, revealing that miR-1273h-5p significantly reduces tumor volume and tumor weight. Conclusions: miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3'-UTR, thus can be used as a potential diagnostic and a novel therapeutic target for GC in clinical practice.

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