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

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.

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

Journal of Translational Medicine ◽

10.1186/s12967-021-03093-w ◽

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.

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CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.706415 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ling Gao ◽

Tingting Xia ◽

Mingde Qin ◽

Xiaofeng Xue ◽

Linhua Jiang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

High Morbidity ◽

Gastric Cancer Cells ◽

Mirna Sponges ◽

Gastric Cancer Cell Proliferation

BackgroundGastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.MethodsCircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK).ResultsThe level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer.ConclusionCollectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.

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lncRNA NEAT1 Inhibits Proliferation, Invasion and Epithelial-mesenchymal Transition of Gastric Cancer Cells by Regulating MiR-129-5p/PBX3 Axis

10.21203/rs.2.22341/v1 ◽

2020 ◽

Author(s):

Hanshu Ji ◽

Xiaoyu Zhang

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Luciferase Reporter ◽

Reporter Assay ◽

Gastric Cancer Cells ◽

Mesenchymal Transition ◽

Lncrna Neat1 ◽

Dual Luciferase Reporter Assay

Abstract Purpose: lncRNA NEAT1 has been reported as a tumor-promoting gene in a variety of tumors, but few studies have explored its role and mechanism in gastric cancer. In the face of increasing incidence of gastric cancer, how to improve the diagnostic accuracy and therapeutic effect of gastric cancer is a major clinical problem. Therefore, we studied the effect and mechanism of lncRNA NEAT1 on the proliferation, invasion and epithelial-mesenchymal transition of gastric cancer cells. To inquiry into the effect of lncRNA NEAT1 on the proliferation, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating miR-129-5p/PBX3 axis. Methods: Totally 63 GC diagnosed and treated in our hospital were selected as the study subjects, whose paired GC tissues and pericarcinomatous tissues were collected as the study specimens after obtaining their consent. QRT-PCR was employed to detect the NEAT1 expression in tissues and cells to analyze the relationship between NEAT1 and clinicopathological data of GC patients. In addition, stable and transient overexpression and inhibition vectors were established and transfected into GC cells HCG-27 and MKN-45. CCK-8, traswell, and flow cytometry were employed to evaluate the proliferation, invasion, and apoptosis of transfected cells. The correlation of miR-129-5p between PBX3 and NEAT1 was assessed using dual luciferase reporter assay, while that between NEAT1 and miR-129-5p was assessed by RNA-binding protein immunoprecipitation (RIP) . Western blot was applied for the detection of apoptosis and EMT related proteins.Results: NEAT1 was overexpressed in GC patients and had a high diagnostic value. The expression of NEAT1 was related to the pathological stage, differentiation degree, tumor size and lymph node metastasis of patients with GC. Down-regulated NEAT1 brought decreased cell proliferation, invasion and EMT, and increased apoptosis. According to dual luciferase reporter assay, NEAT1 could target miR-129-5p, while in turn miR-129-5p could target PBX3. Functional analysis exhibited that miR-129-5p overexpression inhibited PBX3 in GC cells, affecting cell proliferation, invasion, EMT and apoptosis, and rescue experiments demonstrated that these effects were eliminated by up-regulating NEAT1 expression.Conclusion: Inhibition of NEAT1 could mediate miR-129-5p/PBX3 axis to promote apoptosis of GC cells, and reduce cell proliferation, invasion and EMT.

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

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14768374457986 ◽

2017 ◽

Vol 25 (4) ◽

pp. 617-627 ◽

Cited By ~ 27

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.

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

The Journal of Biochemistry ◽

10.1093/jb/mvab050 ◽

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.

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

Cancer Cell International ◽

10.1186/s12935-020-01493-4 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 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.

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

BMC Cancer ◽

10.1186/s12885-021-08227-3 ◽

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.

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CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting miR-196a-3p/AATK Axis

10.21203/rs.3.rs-569952/v1 ◽

2021 ◽

Author(s):

Ling Gao ◽

Tingting Xia ◽

Mingde Qin ◽

Xiaofeng Xue ◽

Linhua Jiang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

High Morbidity ◽

Gastric Cancer Cells ◽

Mirna Sponges ◽

Gastric Cancer Cell Proliferation ◽

Cancer Tissues

Abstract BackgroundGastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical functions in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.MethodsCircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter and RNA pull down assays were used to determine the interaction between circPTK2, miR-196a-3p, AATK.ResultsThe level of circPTK2 was markedly downregulated in gastric cancer tissues. Upregulation of circPTK2 suppressed the proliferation, migration and invasion of gastric cancer cells, while downregulation of circPTK2 exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, circPTK2 overexpression inhibited tumorigenesis in a xenograft mouse model of gastric cancer.ConclusionCollectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation through regulating miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as novel therapeutic target for gastric cancer.

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MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

Molecular Biology of the Cell ◽

10.1091/mbc.e09-05-0386 ◽

2009 ◽

Vol 20 (24) ◽

pp. 5127-5137 ◽

Cited By ~ 27

Author(s):

Kai-Wen Hsu ◽

Rong-Hong Hsieh ◽

Chew-Wun Wu ◽

Chin-Wen Chi ◽

Yan-Hwa Wu Lee ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Progression ◽

Cancer Cells ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Suppressive Effect ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Mesenchymal Transition ◽

Cox 2

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

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

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15016337254632 ◽

2018 ◽

Vol 26 (6) ◽

pp. 847-856 ◽

Cited By ~ 9

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.

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