scholarly journals miR-367-3p enhanced gastric cancer progression by targeting Smad7 to regulate the transforming growth factor-1/Smad3 pathway

2020 ◽  
Author(s):  
Yuan-ming Jing ◽  
Lin Zhang ◽  
Yu Zhang ◽  
guo Jian Wei ◽  
hui Jian Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Luciferase Reporter ◽  
Depth Of Invasion ◽  
Reporter Assays ◽  
Mesenchymal Transformation ◽  
Gastric Cancer Progression ◽  
Tgf Β1

Abstract Several studies have shown that miR-367-3p can function so as to promote or suppress the development of many forms of cancer, but its specific role in gastric cancer (GC) is not fully characterized. In this study, we found that patient GC samples exhibited significantly elevated miR-367-3p expression relative to healthy para-cancerous tissues, and the expression of this miRNA was positively correlated with features of more aggressive disease lymph node metastasis (p=0.025) and depth of invasion (p = 0.047). When miR-367-3p was overexpressed, this led to increased growth, migration, and epithelial-mesenchymal transformation of GC cells, whereas inhibiting this miRNA resulted in the opposite phenotype. Luciferase reporter assays further confirmed the ability of miR-367-3p to target Smad7 and to inhibit its expression. As Smad7 functions to suppress TGF-β1/Smad3 signaling, this miRNA is thus able to enhance TGF-β1/Smad3 signaling, which in turn drives GC progression and feed forward enhancement of this signaling pathway. Together these findings thus offer valuable new insight into the role of miR-367-3p in GC.

scholarly journals ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis

2021 ◽  
Author(s):  
Xiaqiong Mao ◽  
Tao Ji ◽  
Aiguo Liu ◽  
Yunqi Weng
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Suppressor Genes ◽  
Luciferase Reporter ◽  
Diagnosis And Prognosis ◽  
Reporter Assays ◽  
Non Coding Rnas ◽  
Gastric Cancer Progression ◽  
Proliferation And Invasion

Abstract Background Long non-coding RNAs (lncRNAs) play important regulatory roles in the initiation and progression of various cancers. However, the biological roles and the potential mechanisms of lncRNAs in gastric cancers remain unclear. Methods The expression of SNHG22 in gastric cancer was analyzed in public databases (TCGA) and validated via qRT-PCR. SNHG22 knockdown cell lines were construced, and cell proliferation and invasion were analyzed. CHIP and luciferase reporter assays were performed to clarify the transcriptional role of ELK4. RNA pull-down followed MS and RIP assays were employed to identify the interaction between SNHG22 and EZH2. Luciferase reporter assays and RIP assays were used to confirm the regulation of SNHG22 on Notch1 by sponging miR-2003-3p. Results Knockdown of SNHG22 inhibited the proliferation and invasion ability of GC cells. Moreover, we identified that the transcriptional factor, ELK4, could promote SNHG22 expression in GC cells. In addition, using RNA pull-down followed MS assay, we found that SNHG22 directly bound to EZH2 to suppress the expression of tumor suppressor genes. At the same time, SNHG22 sponged miR-200c-3p to increase Notch1 expression. Conclusions Taken together, our findings demonstrated the role of SNHG22 on promoting proliferation and invasion of GC cells. And we revealed a new regulatory mechanism of SNHG22 in GC cells. SNHG22 is a promising lncRNA biomarker for diagnosis and prognosis and a potential target for GC treatment.

scholarly journals MiR-877 suppresses gastric cancer progression by downregulating AQP3

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052090366 ◽  
Author(s):  
Hongyu Zhu ◽  
Yulian Wu ◽  
Muxing Kang ◽  
Bo Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Reporter Assays

Objectives Gastric cancer (GC) is the leading cause of cancer-related deaths worldwide; however, the underlying molecular mechanisms of GC remain unclear. This study investigated the role of the miR-877–AQP3 axis in GC tumorigenesis. Methods The levels of miR-877 expression were measured in GC tissues and cell lines by qRT-PCR. Functional assays were performed to elucidate the role of miR-877 in GC development. Results Our results showed that miR-877 levels were lower in GC tissues and cell lines compared with the corresponding controls. Additionally, reduced miR-877 levels were associated with unfavorable prognoses. Increased miR-877 expression suppressed proliferation, invasion, and epithelial-mesenchymal transition, while promoting apoptosis in GC cells. Luciferase reporter assays showed that aquaporin 3 (AQP3) was a direct downstream target of miR-877. Overexpression of AQP3 partially rescued the tumor suppressive effects of miR-877 in GC cells. Moreover, miR-877 was negatively correlated with AQP3 mRNA expression in GC tissues. Conclusions This study demonstrated that miR-877 plays a suppressive role in GC tumorigenesis by regulating AQP3.

scholarly journals LINC_00355 promotes gastric cancer progression by upregulating PHF19 expression through sponging miR-15a-5p

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jishui Zhang ◽  
Wenhao Lv ◽  
Yagang Liu ◽  
Weihua Fu ◽  
Baosheng Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Phd Finger ◽  
Protein Levels ◽  
The Relationship ◽  
Gastric Cancer Progression ◽  
Dual Luciferase Reporter Assay

Abstract Background Long non-coding RNAs exert vital roles in several types of cancer. The objective of this study was to explore the role of LINC_00355 in gastric cancer (GC) progression and its potential mechanism. Methods The expression levels of LINC_00355 in GC tissues and cells were detected by quantitative real-time PCR, followed by assessing the effects of LINC_00355 knockdown or overexpression on cell properties. Dual-luciferase reporter assay was utilized to identify the relationship between LINC_00355 and microRNA (miR)-15a-5p and miR-15a-5p and PHD finger protein 19 (PHF19), followed by the rescue experiments. Results The results showed that LINC_00355 was highly expressed in GC tissues and cells compared with the corresponding control. LINC_00355 knockdown decreased the viability, migration, and invasion and increased the accumulation of GC cells in G1 phase and apoptosis. Meanwhile, LINC_00355 downregulation markedly increased cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase protein levels, whereas decreased cyclin D1, cyclin E, matrix metalloproteinase (MMP) 9, MMP2, and N-cadherin protein levels in GC cells. However, LINC_00355 overexpression had the opposite effects. It was verified that LINC_00355 upregulated the expression of PHF19 through sponging miR-15a-5p. Furthermore, PHF19 overexpression reversed the effect of LINC_00355 knockdown on GC cell properties, including cell viability, migration, invasion, and apoptosis. Conclusions Collectively, these results suggest that LINC_00355 promotes GC progression by up-regulating PHF19 through sponging miR-15a-5p. Our findings may provide an important clinical basis for reversing the malignant phenotype of GC.

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

scholarly journals The Emerging Role of GC-MSCs in the Gastric Cancer Microenvironment: From Tumor to Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Wound Repair ◽  
Critical Role ◽  
The Novel ◽  
Potential Biomarker ◽  
Underlying Mechanisms ◽  
Gastric Cancer Progression

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.

scholarly journals Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Fei Liu ◽  
Jianxin Fu ◽  
Kirk Bergstrom ◽  
Xindi Shan ◽  
J. Michael McDaniel ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Gastric Epithelium ◽  
Tn Antigen ◽  
Gastric Mucus ◽  
Truncated Form ◽  
Gastric Cancer Patients ◽  
Gastric Cancer Progression

Core 1–derived mucin-type O-glycans (O-glycans) are a major component of gastric mucus with an unclear role. To address this, we generated mice lacking gastric epithelial O-glycans (GEC C1galt1−/−). GEC C1galt1−/− mice exhibited spontaneous gastritis that progressed to adenocarcinoma with ∼80% penetrance by 1 yr. GEC C1galt1−/− gastric epithelium exhibited defective expression of a major mucus forming O-glycoprotein Muc5AC relative to WT controls, which was associated with impaired gastric acid homeostasis. Inflammation and tumorigenesis in GEC C1galt1−/− stomach were concurrent with activation of caspases 1 and 11 (Casp1/11)–dependent inflammasome. GEC C1galt1−/− mice genetically lacking Casp1/11 had reduced gastritis and gastric cancer progression. Notably, expression of Tn antigen, a truncated form of O-glycan, and CASP1 activation was associated with tumor progression in gastric cancer patients. These results reveal a critical role of O-glycosylation in gastric homeostasis and the protection of the gastric mucosa from Casp1-mediated gastric inflammation and cancer.

scholarly journals MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yixun Lu ◽  
Benlong Zhang ◽  
Baohua Wang ◽  
Di Wu ◽  
Chuang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues ◽  
Gastric Cancer Progression

Abstract Background Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. Methods Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. Results GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. Conclusions MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

scholarly journals LncRNA ELFN1-AS1 Upregulates TRIM29 to Promote Gastric Cancer Progression by Suppressing miR-211-3p

2021 ◽  
Author(s):  
Jinxi Huang ◽  
Weiwei Yuan ◽  
Beibei Chen ◽  
Gaofeng Li ◽  
Xiaobing Chen
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Vitality ◽  
Reverse Transcription Quantitative Pcr ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Cancer Tissues

Abstract BackgroundExtracellular leucine rich repeat and fibronectin type III domain containing 1-antisense RNA 1 (ELFN1-AS1) was upregulated in tumors. Nevertheless, the biological functions of ELFN1-AS1 in gastric cancer are not fully understood.MethodsThe ELFN1-AS1, miR-211-3p and TRIM29 expression levels were determined by reverse transcription-quantitative PCR. CCK8, EDU and colony formation assays were done to test the GC cell vitality. The migratory and invasive capabilities of GC cells were further measured by transwell invasion and cell scratch assays. The ceRNA activity of ELFN1-AS1 for TRIM29 via miR-211-3pp was ascertained through pull down, RIP and luciferase reporter assays.ResultsELFN1-AS1 and TRIM29 were robustly expressed in gastric cancer tissues and negatively associated overall survival time of patients. The ELFN1-AS1 silence blocked the proliferation, migration and invasion of GC cells. The oncogenic role of ELFN1-AS1 was recognized to be modulated by miR-211-3pp, which competitively bind to 3'UTR TRIM29 and resulted in the reduced expression of TRIM29.ConclusionELFN1-AS1 maintained the tumorigensis of GC cells by ELFN1-AS1/miR-211-3pp/TRIM29 axis, suggesting that intervention targeting this axis may be warranted for GC treatment.

scholarly journals Microbiome signatures in a fast and slow progressing gastric cancer murine model and their contribution to gastric carcinogenesis

2020 ◽  
Author(s):  
Prerna Bali ◽  
Joanna Coker ◽  
Ivonne Lozano-Pope ◽  
Karsten Zengler ◽  
Marygorret Obonyo
Keyword(s):  
Gastric Cancer ◽  
Microbial Diversity ◽  
Cancer Progression ◽  
Double Knockout ◽  
Histological Data ◽  
H Pylori ◽  
Faster Development ◽  
Gastric Cancer Progression ◽  
Development Of Gastric Cancer

AbstractGastric cancer is the third most common cancer in the world and Helicobacter spp. being one of the main factors responsible for development of cancer. Alongside Helicobacter the microbiota of the stomach mucosa may also play an important role in gastric cancer progression. Previously we had established that MyD88 deficient mice rapidly progressed to neoplasia when infected with H. felis. Thus, in order to assess the role of microbiota in gastric cancer progression we measured the changes in microbial diversity of the stomach in mice with different genotypic backgrounds (Wild type (WT), MyD88 deficient (MyD88−/−), mice deficient in the Toll/IL-1R (TIR) domain-containing adaptor-inducing interferon-β (TRIF, Triflps2), and MyD88 and Trif deficient (MyD88−/− and Trif−/−)double knockout (DKO) mice), both in uninfected and Helicobacter infected mice and its correlation of these changes with gastric cancer progression. We observed that there was an overall reduction in microbial diversity post infection with H. felis across all genotypes. Campylobacterales were observed in all infected mice, with marked reduction in abundance at 3 and 6 months in MyD88−/− mice. This low abundance of H. pylori could facilitate dominance of other organisms of microbiome like Lactobacilliales. A sharp increase in Lactobacilliales in infected MyD88−/− and DKO mice at 3 and 6 months was observed as compared to Trif−/− and WT mice suggesting its possible role in gastric cancer progression. This was further reinforced upon comparison of Lactobacillus ratio with histological data suggesting that Lactobacillales is closely associated with Helicobacter infection and gastric cancer progression. Thus, this study firstly suggests that difference in genotypes could define the stomach microbiome and make it more susceptible to development of gastric cancer upon Helicobacter infections. Secondly the increase in Lactobacillales could contribute to faster development of gastric cancer and serve as a probable bio marker for fast progressing form of gastric cancer.

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