scholarly journals MicroRNA-491-5p inhibit gastric cancer development by targeting EMT, cell adhesion genes and IFITM2

2020 ◽  
Author(s):  
Zhijian Wei ◽  
Lixiang Zhang ◽  
Angqing Li ◽  
Chuanhong Li ◽  
Wenxiu Han ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Tumor Suppressor ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Different Types ◽  
High Level

Abstract Gastric cancer (GC) is one of the deadliest cancers in China. And, it can be regulated by MicroRNAs (miRNAs) generally. miR-491-5p function as a tumor suppressor in different types of cancer, but we still don’t know the role of miR-491-5p in gastric cancer. In this study, we found that high level of miR-491-5p caused a weak cell proliferation, migration and invasion abilities. In order to explore the role of miR-491-5p in vivo, we set a xenograft mouse model, and also found that high level of miR-491-5p suppressed tumor growth. Moreover, we found that miR-491-5p regulate the tumor development thought regulate the expression of EMT, cell adhesion genes and IFITM2. These data show that miR-491-5p function as a tumor suppressor in GC both in vitro and in vivo .

scholarly journals MicroRNA-491-5p inhibit gastric cancer development by targeting EMT, cell adhesion genes and IFITM2

2020 ◽  
Author(s):  
zhijian Wei ◽  
lixiang Zhang ◽  
angqing Li ◽  
chuanhong li ◽  
wenxiu han ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Tumor Suppressor ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Western Blot Assay ◽  
Mesenchymal Transition ◽  
High Level

Abstract Background: Gastric cancer (GC) is one of the deadliest cancers in China. And, it can be regulated by MicroRNAs (miRNAs) generally. miR-491-5p function as a tumor suppressor in different types of cancer, but we still don’t know the role of miR-491-5p in gastric cancer. Methods: Functional experiments including CCK-8 assay and transwell assay were performed. Furthermore, the underlying mechanism was explored through qRT-PCR and western blot assay. In addition, the function of miR-491-5p was also identified in vivo.Results: In this study, we found that high level of miR-491-5p caused a weak cell proliferation, migration and invasion abilities. In order to explore the role of miR-491-5p in vivo, we set a xenograft mouse model, and also found that high level of miR-491-5p suppressed tumor growth. Moreover, we found that miR-491-5p regulate the tumor development thought regulate the expression of EMT(Epithelial-mesenchymal transition), cell adhesion genes and IFITM2. Conclusions: These data show that miR-491-5p function as a tumor suppressor in GC both in vitro and in vivo.

scholarly journals Hypermethylation of DHRS3 as a Novel Tumor Suppressor Involved in Tumor Growth and Prognosis in Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Sha Sumei ◽  
Kong Xiangyun ◽  
Chen Fenrong ◽  
Sun Xueguang ◽  
Hu Sijun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Human Cancer ◽  
Methylation Status ◽  
Ectopic Expression ◽  
Survival Times

Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

scholarly journals NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

2020 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Yan He ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Hippo Pathway ◽  
Critical Role ◽  
Xenograft Model ◽  
Migration And Invasion

Abstract Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

scholarly journals MiR-1188 at the imprinted Dlk1-Dio3 domain acts as a tumor suppressor in hepatoma cells

2015 ◽  
Vol 26 (8) ◽  
pp. 1416-1427 ◽  
Author(s):  
Wei Cui ◽  
Zhijun Huang ◽  
Hongjuan He ◽  
Ning Gu ◽  
Geng Qin ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Normal Liver ◽  
Hepatoma Cells ◽  
Genomic Region ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Profiling Analysis

The aberrant expression of microRNAs (miRNAs) has frequently been reported in cancer studies; miRNAs play roles in development, progression, metastasis, and prognosis. Recent studies indicate that the miRNAs within the Dlk1-Dio3 genomic region are involved in the development of liver cancer, but the role of miR-1188 in hepatocellular carcinoma (HCC) and the pathway by which it exerts its function remain largely unknown. Here we demonstrate that miR-1188 is significantly down-regulated in mouse hepatoma cells compared with normal liver tissues. Enhanced miR-1188 suppresses cell proliferation, migration, and invasion in vitro and inhibits the tumor growth of HCC cells in vivo. Moreover, overexpressed miR-1188 promotes apoptosis, enhances caspase-3 activity, and also up-regulates the expression of Bax and p53. MiR-1188 directly targets and negatively regulates Bcl-2 and Sp1. Silencing of Bcl-2 and Sp1 exactly copies the proapoptotic and anti-invasive effects of miR-1188, respectively. The expression of apoptosis- and invasion-related genes, such as Vegfa, Fgfr1, and Rprd1b, decreases after enhancement of miR-1188, as determined by gene expression profiling analysis. Taken together, our results highlight an important role for miR-1188 as a tumor suppressor in hepatoma cells and imply its potential role in cancer therapy.

scholarly journals MiR-223 Promotes Tumor Progression via Targeting RhoB in Gastric Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
You Hu ◽  
Bin Yi ◽  
Xin Chen ◽  
Lu Xu ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Cellular Mechanisms ◽  
Borrmann Type ◽  
Potential Biomarker

Gastric cancer (GC) is among the most prevalent causes of cancer-related death globally. MiR-223 has been implicated in a variety of cellular mechanisms linked to cancer progression. However, the miR-223 expressions and its function in GC are unknown. We discovered that miR-223 expression was raised in GC tissues in comparison with nearby normal tissues in this investigation. Additionally, multiplied miR-223 expression was strongly linked with TNM stage ( p = 0.022 ), live metastasis ( p = 0.004 ),lymph node metastasis ( p = 0.004 ),and Borrmann type and was associated with an unfavorable prognostic for patients with GC. Furthermore, suppressing miR-223 significantly increased cell death and prevented cell migration and invasion in vitro. Additionally, miR-223 silencing decreased tumor development in vivo. Additionally, we discovered that miR-223 enhanced GC development by specifically targeting RhoB. In summary, our findings reveal that miR-223 increases tumor progression in GC by targeting RhoB, suggesting that it could serve to be a potential biomarker for the prediction of the disease.

scholarly journals The Interaction Between Long Non-Coding RNA LINC01564 and POU2F1 Promotes the Proliferation and Metastasis of Gastric Cancer

2021 ◽  
Author(s):  
Jixu Wang ◽  
Futao Hou ◽  
Lusheng Tang ◽  
Ke Xiao ◽  
Tengfei Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Tumor Development ◽  
Transcription Activation ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Proliferation And Metastasis ◽  
And Migration

Abstract Background: An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) serve as key regulators in tumor development and progression. However, only a few lncRNAs have been functionally characterized in gastric cancer (GC). Methods: Bioinformatics analysis was conducted to find lncRNAs that are associated with GC metastasis. RNA FISH, RIP, and RNA pull down assays were used to study the complementary binding of LINC01564 complementary to the 3’UTR of transcription factor POU2F1. The transcription activation of LINC01564 by POU2F1 as a transcription factor was examined by ChIP assay. In vitro assays such as MTT, cell invasion assay, and clonogenic assay were conducted to examined the impacts of LINC01564 and POU2F1 on GC cell proliferation and invasion. Experiments in vivo were performed to access the impacts of LINC01564 and POU2F1 on GC metastasis. Results: The results showed that LINC01564 complementary bound to the 3’UTR of POU2F1 to form an RNA duplex, whereby stabilizing POU2F1 mRNA and increasing the enrichment in cells. The level of LINC01564 was also increased by POU2F1 through transcription activation. In vitro assays showed that LINC01564 promoted the proliferation, invasion and migration of GC cells through increasing POU2F1. In vivo experiments indicate the promotion of GC proliferation and metastasis by the interaction between LINC01564 and POU2F1. Conclusion: Taken together, our results indicate that the interaction between LINC01564 and POU2F1 promotes the proliferation, migration and invasion of GC cells.

scholarly journals HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chenlong Song ◽  
Chongzhi Zhou
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Lung Metastasis ◽  
Essential Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Signaling Axis

Abstract Background Homeobox A10 (HOXA10) belongs to the HOX gene family, which plays an essential role in embryonic development and tumor progression. We previously demonstrated that HOXA10 was significantly upregulated in gastric cancer (GC) and promoted GC cell proliferation. This study was designed to investigate the role of HOXA10 in GC metastasis and explore the underlying mechanism. Methods Immunohistochemistry (IHC) was used to evaluate the expression of HOXA10 in GC. In vitro cell migration and invasion assays as well as in vivo mice metastatic models were utilized to investigate the effects of HOXA10 on GC metastasis. GSEA, western blot, qRT-PCR and confocal immunofluorescence experiments preliminarily analyzed the relationship between HOXA10 and EMT. ChIP-qPCR, dual-luciferase reporter (DLR), co-immunoprecipitation (CoIP), colorimetric m6A assay and mice lung metastasis rescue models were performed to explore the mechanism by which HOXA10 accelerated the EMT process in GC. Results In this study, we demonstrated HOXA10 was upregulated in GC patients and the difference was even more pronounced in patients with lymph node metastasis (LNM) than without. Functionally, HOXA10 promoted migration and invasion of GC cells in vitro and accelerated lung metastasis in vivo. EMT was an important mechanism responsible for HOXA10-involved metastasis. Mechanistically, we revealed HOXA10 enriched in the TGFB2 promoter region, promoted transcription, increased secretion, thus triggered the activation of TGFβ/Smad signaling with subsequent enhancement of Smad2/3 nuclear expression. Moreover, HOXA10 upregulation elevated m6A level and METTL3 expression in GC cells possible by regulating the TGFB2/Smad pathway. CoIP and ChIP-qPCR experiments demonstrated that Smad proteins played an important role in mediating METTL3 expression. Furthermore, we found HOXA10 and METTL3 were clinically relevant, and METTL3 was responsible for the HOXA10-mediated EMT process by performing rescue experiments with western blot and in vivo mice lung metastatic models. Conclusions Our findings indicated the essential role of the HOXA10/TGFB2/Smad/METTL3 signaling axis in GC progression and metastasis.

scholarly journals The role of TRPV1 ion channels in the suppression of gastric cancer development

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Nannan Gao ◽  
Feng Yang ◽  
Siyuan Chen ◽  
Hanxing Wan ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Size ◽  
Peritoneal Dissemination ◽  
Migration And Invasion ◽  
Transient Receptor Potential Vanilloid ◽  
Aberrant Expression ◽  
Trpv1 Channels

Abstract Background Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association between transient receptor potential vanilloid receptor 1 (TRPV1) channels and gastric cancer (GC) has not yet been explored. Herein, we sought to determine the role of TRPV1 channels in the development of GC and to elucidate the underlying molecular mechanisms involved therein. Methods Immunohistochemistry, qPCR, Western blot, immunofluorescence assays were used to detect the mRNA and protein expression of TRPV1 in GC cells and tissues, and the clinical significance of TRPV1 in GC was also studied by clinicopathologic analysis. CCK8, colony formation, flow cytometry assays were used to detect the proliferation and survival of GC cells, while transwell assay was used to detect migration and invasion of GC cells in vitro. Tumor xenograft and peritoneal dissemination assays in nude mice were used to examine the role of TRPV1 in GC development in vivo. Results TRPV1 expression was significantly downregulated in human primary GC tissues compared to their adjacent tissues. The decreased expression of TRPV1 proteins in GC tissues was positively correlated with tumor size, histological grade, lymphatic metastasis, clinical stage, and was strongly correlated with poor prognosis of GC patients. Moreover, the expression of TRPV1 was closely correlated with Ki67, VEGFR, and E-cadherin, all of which are the well-known cancer markers for proliferation and metastasis. TRPV1 proteins were predominately expressed on the plasma membrane in several GC cell lines. TRPV1 overexpression blocked cell cycle at G1 phase to inhibit GC cell proliferation and attenuated migration and invasion of GC cells in vitro, but TRPV1 knockdown increased these parameters. TRPV1 significantly reduced gastric tumor size, number and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression in GC cells increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, while TRPV1 knockdown induced the opposite effects. Conclusions TRPV1 uniquely suppresses GC development through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival of human GC patients. Thus, TRPV1 upregulation and its downstream signaling may represent a promising target for GC prevention and therapy.

scholarly journals MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Naveenkumar Perumal ◽  
Ranjana K. Kanchan ◽  
David Doss ◽  
Noah Bastola ◽  
Pranita Atri ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cancer Cell ◽  
Migration And Invasion ◽  
Stem Cell Markers ◽  
Cancer Cell Proliferation ◽  
Group 3

AbstractHaploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors. First, we learned that miR-212-3p undergoes epigenetic silencing by histone modifications in group 3 tumors. Restoring its expression reduced cancer cell proliferation, migration, colony formation, and wound healing in vitro and attenuated tumor burden and improved survival in vivo. MiR-212-3p also triggered c-Myc destabilization and degradation, leading to elevated apoptosis. We then isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors and associated with poor survival. NFIB silencing reduced cancer cell proliferation, migration, and invasion. Concurrently, reduced medullosphere formation and stem cell markers (Nanog, Oct4, Sox2, CD133) were noted. These results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and identify a novel oncogenic target implicated in metastasis and tumor recurrence.

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