scholarly journals circABCB10 Promotes Malignant Progression of Gastric Cancer Cells by Preventing the Degradation of MYC

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yingchun Zhang ◽  
Yong Zhou ◽  
Fang Wei
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Malignant Progression ◽  
Luciferase Reporter ◽  
Regulatory Effect ◽  
Gastric Cancer Cells ◽  
Subcutaneous Tumor ◽  
Tumor Bearing ◽  
Gene Assay ◽  
Cancer Tissues

Objective. To investigate the role of circABCB10 in gastric cancer and the molecular mechanism of promoting malignant progression of gastric cancer cells by preventing the degradation of MYC by hsa-miR-1252-5p. Methods. The expression of circABCB10 in gastric cancer tissues and cells was detected by real-time quantitative PCR. MTT, Transwell, clone formation, and TUNEL assay were used to detect the effects of circABCB10 on the proliferation, invasion, and apoptosis of gastric cancer cells. A subcutaneous tumor-bearing model was established to study the inhibitory effect of knockdown circABCB10 on gastric cancer proliferation. The dual luciferase reporter gene assay and RNA pull-down assay were used to verify the regulatory effect of circABCB10 on miR-1252-5p and the regulatory effect of miR-1252-5p on MYC. Results. Compared with paracancerous tissues and gastric mucosal epithelial cells, the expression of circABCB10 was significantly increased in human gastric cancer tissues and gastric cancer cells. circABCB10 knockout significantly decreased cell viability and invasion ability and promoted cell apoptosis ( P < 0.01 ). Subcutaneous tumor-bearing experiments in nude mice demonstrated that circABCB10 knockdown inhibited the proliferation of gastric cancer cells. circABCB10 can act as a sponge for miR-1252-5p in gastric cancer cells. Meanwhile, MYC is the target gene of miR-1252-5p. Overexpression of miR-1252-5p and knockdown of MYC reversed the promoting effect of circABCB10 on gastric cancer. Conclusion. circABCB10 can promote the proliferation, invasion, and clonal formation of gastric cancer cells by targeting miR-1252-5p and upregulating the expression of MYC. circABCB10/miR-1252-5p/MYC constitutes the regulatory mechanism of ceRNA.

scholarly journals Circ_002117 binds to microRNA-370 and promotes endoplasmic reticulum stress-induced apoptosis in gastric cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nan Zhou ◽  
Hui Qiao ◽  
Miaomiao Zeng ◽  
Lei Yang ◽  
Yongning Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Gene Assay ◽  
Induced Apoptosis ◽  
Cancer Tissues

Abstract Background Mounting evidence implicates circular RNAs (circRNAs) in various biological processes during cancer progression. Gastric cancer is a main cause of cancer-related deaths worldwide. Herein, we aimed at investigating whether circ_002117 mediates gastric cancer progression through endoplasmic reticulum (ER) stress. Methods Bioinformatics analysis detected differentially expressed circRNAs and their target miRNA candidates, and RT-qPCR was performed to detect expression of circ_002117, microRNA (miRNA)-370 and HERPUD1 in gastric cancer tissues and cells. Gastric cancer cells were transfected with plasmids and their proliferative ability and apoptosis were detected with gain- and loss-of-function assay. The ER of treated cells was observed under a transmission electron microscope. Dual-luciferase reporter gene assay and RIP were performed to detect the interaction between HEPRUD1, miR-370 and circ_002117-treated cells were injected into mice to establish xenograft tumor model. Results Circ_002117 and HEPRUD1 were poorly expressed whereas miR-370 was highly expressed in clinical cancer tissues and cells. Circ_002117 was indicated to target and suppress miR-370 expression, while HERPUD1 was directly targeted by miR-370. Circ_002117 overexpression or miR-370 deficiency promoted ER stress-induced apoptosis and decreased proliferation of gastric cancer cells, which was reversed by silencing of HEPRUD1. Circ_002117 overexpression or miR-370 depletion significantly suppressed gastric cancer tumorigenesis in vivo. Conclusions Taken altogether, circ_002117 facilitated ER stress-induced apoptosis in gastric cancer by upregulating HERPUD1 through miR-370 inhibition.

scholarly journals MicroRNA-154 Inhibits the Growth and Invasion of Gastric Cancer Cells by Targeting DIXDC1/WNT Signaling

2018 ◽  
Vol 26 (6) ◽  
pp. 847-856 ◽  
Author(s):  
Jifu Song ◽  
Zhibin Guan ◽  
Maojiang Li ◽  
Sha Sha ◽  
Chao Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Inverse Correlation ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Cancer Cell Growth ◽  
Cancer Tissues

MicroRNAs (miRNAs) have emerged as pivotal regulators of the development and progression of gastric cancer. Studies have shown that miR-154 is a novel cancer-associated miRNA involved in various cancers. However, the role of miR-154 in gastric cancer remains unknown. Here we aimed to investigate the biological function and the potential molecular mechanism of miR-154 in gastric cancer. We found that miR-154 was significantly downregulated in gastric cancer tissues and cell lines. The overexpression of miR-154 significantly repressed the growth and invasion of gastric cancer cells. Bioinformatics analysis and Dual-Luciferase Reporter Assay data showed that miR-154 directly targeted the 3′-untranslated region of Dishevelled‐Axin domain containing 1 (DIXDC1). Real-time quantitative polymerase chain reaction and Western blot analyses showed that miR-154 overexpression inhibited DIXDC1 expression. An inverse correlation of miR-154 and DIXDC1 was also demonstrated in gastric cancer specimens. Overexpression of miR-154 also significantly suppressed the activation of WNT signaling. Moreover, restoration of DIXDC1 expression significantly reversed the inhibitory effect of miR-154 overexpression on the cell proliferation, invasion, and WNT signaling in gastric cancer cells. Overall, these results suggest that miR-154 inhibits gastric cancer cell growth and invasion by targeting DIXDC1 and could serve as a potential therapeutic target for the treatment of gastric cancer.

scholarly journals MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Chunsheng Li ◽  
Jingrong Dong ◽  
Zhenqi Han ◽  
Kai Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

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 p38MAPK Signaling Enhances Glycolysis Through the Up-Regulation of the Glucose Transporter GLUT-4 in Gastric Cancer Cells

2015 ◽  
Vol 36 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Jingjing Liu ◽  
Dacheng Wen ◽  
Xuedong Fang ◽  
Xudong Wang ◽  
Tianzhou Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Glucose Uptake ◽  
Cancer Cells ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Glut 4 ◽  
Cancer Tissues

Background/Aims: Previous studies have shown that p38MAPK is involved in gastric cancer, yet the underlying mechanism remains unclear. Methods: q-PCR, Western blot and immunohistochemistry were used to explore the expression of PP2A and the phosphorylation of p38MAPK in gastric cancer tissues and normal gastric tissues. Activated p38MAPK in the gastric cancer cell line MKN45 using activator, then q-PCR, glucose uptake assay and colony formation assay were performed to determine whether p38MAPK promotes gastric cancer through the enhancement of glycolysis. After transfection of p38MAPK dominant negative mutation (p38DN) into MKN45 cells or MKN45 cells treated with an inhibitor of p38MAPK, Western blot was performed to detect the expression of GLUT-4. The knock down of MEF2α in MKN45 cells by siRNA was followed by Western blot and luciferase reporter assay to investigate the underlying mechanism of the role of p38MAPK in the promotion of gastric cancer. Finally, q-PCR, Western blot and immunohistochemistry were performed to examine GLUT-4 expression in gastric cancer tissues and normal gastric tissues. Results: We found that p38MAPK activation significantly increases GLUT-4 expression and promotes glucose uptake and cell growth in gastric cancer cells. Inhibition of p38MAPK abrogates the up-regulation of GLUT-4. MEF2α knockdown abolishes p38MAPK-mediated GLUT-4 up-regulation. PP2A, an inhibitor of p38MAPK, is down-regulated in gastric cancer tissues, which might contribute to the activation of p38MAPK. Conclusions: Our data indicate that the abnormal activation of p38MAPK promotes glycolysis within gastric cancer cells through the upregulation of GLUT-4 in a MEF2a-dependent manner.

HOTAIR Competitively Binds MiRNA330 as a Molecular Sponge to Increase the Resistance of Gastric Cancer to Trastuzumab

2020 ◽  
Vol 20 (9) ◽  
pp. 700-709 ◽  
Author(s):  
Liangyu Bie ◽  
Suxia Luo ◽  
Dan Li ◽  
Yan Wei ◽  
Yu Mu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Lentiviral Vector ◽  
Luciferase Reporter ◽  
Tumor Proliferation ◽  
Trastuzumab Resistance ◽  
Luciferase Reporter Gene ◽  
Gastric Cancer Cells ◽  
Strong Expression ◽  
Gene Assay

Background: HOTAIR, one of the most widely studied long non-coding RNAs in tumors, is closely related to tumor proliferation, migration, invasion and chemoresistance. Objective: Here, we studied the mechanism behind proliferation and chemoresistance processes. Methods: A total of 75 samples were collected from patients who underwent surgical resection of their gastric cancer and received trastuzumab treatment. Primary cells were isolated and cultured. We also developed a cell line overexpressing HOTAIR by constructing a lentiviral vector. These cell lines were studied using an array of established biomolecular methods. Results: We found that HOTAIR levels were inversely associated with sensitivity to trastuzumab in gastric cancer and that overexpression of HOTAIR can promote the proliferation and invasion of gastric cancer cells. The sensitivity of cells overexpressing HOTAIR to two different types of human epidermal growth factor receptor 2 (HER2) inhibitors (trastuzumab and afatinib) showed that overexpression of HOTAIR is specific for trastuzumab resistance. Furthermore, luciferase reporter gene assay and western blot assay showed that there is a HOTAIR-miRNA330-ERBB4 competitive endogenous RNA regulatory network with miRNA330 as the core. Conclusion: HOTAIR can not only promote tumor proliferation but also enhance the resistance of tumor cells to drugs. Our experimental data not only showed strong expression of HOTAIR in gastric cancer, but also that strong expression of HOTAIR caused the sensitivity of gastric cancer cells to trastuzumab, which is a useful reference for postoperative medication.

LINC01207 is up-regulated in gastric cancer tissues and promotes disease progression by regulating miR-671-5p/DDX5 axis

2021 ◽  
Author(s):  
Hongquan Liu ◽  
Xiaoyu Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Downstream Target ◽  
Proliferation And Metastasis ◽  
Cancer Tissues

Abstract LINC01207 is involved in the progression of some cancers. This study was designed to delve into the biological function and mechanism of LINC01207 in gastric cancer. qPCR was adopted to examine the expression levels of LINC01207, miR-671-5p, DDX5 mRNA in gastric cancer tissues and cells. After LINC01207 was overexpressed or depleted, MTT and BrdU assays were conducted to detect cell proliferation. Transwell assay was employed to detect cell migration and invasion. Western blot was used to detect the expression of DDX5 protein in cells. Bioinformatics analysis, luciferase reporter assay and RNA pull-down assay were performed to predict and validate the binding site between miR-671-5p and LINC01207 or DDX5. LINC01207, DDX5 mRNA were up-regulated in gastric cancer, while miR-671-5p was down-regulated; high expression of LINC01207 and transfection of miR-671-5p inhibitors facilitated the proliferation of gastric cancer cells; however, knocking down LINC01207 and the overexpression of miR-671-5p mimics had opposite biological effects. LINC01207 and miR-671-5p were interacted and miR-671-5p was negatively regulated by LINC01207. MiR-671-5p could reverse the function of LINC01207. DDX5 was a downstream target of miR-671-5p and was positively modulated by LINC01207. LINC01207 promotes the proliferation and metastasis of gastric cancer cells by regulating miR-671-5p/DDX5 axis.

scholarly journals LncRNA SNHG7 Regulates Gastric Cancer Progression by miR-485-5p

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhongsong Zhao ◽  
Xueping Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Gastric Cancer Cells ◽  
Cancer Tissues ◽  
Gastric Cancer Progression ◽  
Dual Luciferase Reporter Assay

Background. Long noncoding ribonucleic acids (lncRNAs) were closely related to the development of gastric cancer. This study investigated the effect of SNHG7 on gastric cancer progression and its potential molecular mechanism. Methods. SNHG7 and microRNA-485-5p (miR-485-5p) expressions in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), wound healing, and transwell experiments were used to detect cell proliferation, migration, and invasion. The dual luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Pearson’s correlation analysis were used to confirm the relationship between SNHG7 and miR-485-5p. Results. SNHG7 expression was increased in human gastric cancer tissues and cells. Knockdown of SNHG7 could notably inhibit the gastric cancer cells proliferation, migration, and invasion. The dual-luciferase reporter assay and RIP experiments proved that miR-485-5p was a direct target of SNHG7. At the same time, further experiments demonstrated that miR-485-5p inhibition reversed the suppression of SNHG7 knockdown on gastric cancer cells proliferation, migration, and invasion. Conclusions. SNHG7 knockdown could hamper gastric cancer progression via inhibiting miR-485-5p expression, providing a novel understanding for gastric cancer development.

scholarly journals miR-223-3p promotes cell proliferation and invasion by targeting Arid1a in gastric cancer

2020 ◽  
Vol 52 (2) ◽  
pp. 150-159 ◽  
Author(s):  
Yiping Zhu ◽  
Kai Li ◽  
Liang Yan ◽  
Yang He ◽  
Lu Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Downstream Signaling ◽  
Cell Progression ◽  
Cancer Tissues ◽  
Tumor Invasion Depth ◽  
Proliferation And Invasion

Abstract Accumulating evidence has indicated that microRNAs can regulate downstream signaling pathways and play an important role in various tumors. In this study, we found that miR-223-3p was differentially expressed in 40 paired gastric cancer tissues and adjacent tissues and that miR-223-3p was positively correlated with tumor invasion depth and lymph node metastasis. Luciferase reporter assay confirmed that Arid1a was the target gene of miR-223-3p. Functional assays showed that miR-223-3p promoted the proliferation and invasion of gastric cancer cells by regulating the expression of Arid1a. We also confirmed that miR-223-3p regulated the growth of gastric cancer cells in vivo, while an antagomir against miR-223-3p significantly inhibited tumor growth. In conclusion, our results demonstrated that miR-223-3p inhibits gastric cancer cell progression by decreasing the expression of Arid1a. Therefore, miR-223-3p may act as a potential therapeutic target for patients with gastric cancer.

scholarly journals LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p

2017 ◽  
Vol 42 (3) ◽  
pp. 999-1012 ◽  
Author(s):  
Kai Yan ◽  
Jie Tian ◽  
Wenzheng Shi ◽  
Hao Xia ◽  
Yuanfang Zhu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Luciferase Reporter ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Gastric Cancer Cells ◽  
Node Metastasis ◽  
Reporter Assays ◽  
Cancer Tissues

Background/Amis: Long non-coding RNAs (lncRNAs), a novel class of transcripts, have been shown to play critical roles in diverse cellular biological processes, including tumorigenesis. Small nucleolar RNA host gene 6 (SNHG6) regulates various biological processes in cancer cells. However, the biological role of SNHG6 in gastric cancer still remains to be explored. The aim of this study is to investigate the characteristic of the SNHG6 in gastric cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of SNHG6 in gastric cancer tissues and cell lines. MTT assays, colony formation assays were used to determine the impact of SNHG6 on tumorigenesis . Flow cytometric analysis of cell cycle and apoptosis was performed to measure the effect of SNHG6 on cell cycle and apoptosis rate. Transwell assay was performed to measure the effect of SNHG6 on cell migration. Western blotting and immunofuorescence were utilized to examine the effect of SNHG6 on epithelial-mesenchymal transition (EMT) of GC cells. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), RNA-pulldown and luciferase reporter assays were employed to dissect molecular mechanisms. Results: In this study, we revealed that SNHG6 was overexpressed in gastric cancer tissues and cell lines. High expression levels of SNHG6 wereassociated with invasion depth, lymph node metastasis, distant metastasis and tumor/node/metastasis (TNM) stage, and predicted poor prognosis. Loss-of-function assays revealed that silenced SNHG6 obviously inhibited gastric cancer cell growth, weakened cell migration capacity and suppressed the EMT processes of gastric cancer cells. Additionally, ChIP, RIP, RNA-pulldown and luciferase reporter assays evidenced that SNHG6 could epigenetically silenced p27 and could competitively sponging miR-101-3p thereby regulating zinc finger E-box-binding homeobox 1 (ZEB1). Conclusion: In summary, our findings demonstrated that SNHG6 acted as an oncogene in gastric cancer cells through regulating miR-101-3p/ZEB1 at a post-transcriptional level and silencing expression at a transcriptional level by recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p27. SNHG6 might serve as a candidate prognostic biomarker and a target for novel therapies of gastric cancer patients.

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