FOXF2-Mediated lncRNA LINC02532 Promotes Gastric Cancer Cell Migration and Invasion By Decreasing SOX7 mRNA Stability

Abstract Background LncRNAs are known to play a crucial role in the initiation and progression of human diseases, especially cancers. Our previous study demonstrated that dysregulation of LINC02532 facilitated the malignant phenotype of gastric cancer (GC). However, the potential molecular mechanisms regarding the upstream and downstream regulation of LINC02532 in GC progression remain unclear. Methods RNA-Seq and clinical data from public databases were used for gene expression and clinical analyses. The subcellular location of LINC02532 was predicted by the bioinformatics tools and further validated by the RNA-Fluorescence in situ hybridization (FISH) assay. The effect of FOXF2/LINC02532/SOX7 axis in GC cell migration and invasion was evaluated using in vitro and in vivo assays. The transcriptional regulation role of FOXF2 and the mRNA stability of SOX7 were explored by dual-luciferase reporter assay and Actinomycin-D drug assay. Results We found that high LINC02532 expression was associated with poor prognosis of GC. Furthermore, a Cox regression model indicated that LINC02532 was an independent prognostic factor for GC patients. Using in vitro and in vivo assays, we found that LINC02532 promoted GC cell migration and invasion, as well as tumour growth and metastasis in nude mice. Mechanistically, LINC02532 decreased SOX7 mRNA stability by binding to its 3’UTR, resulting in reduced SOX7 expression. In addition, FOXF2 was identified as a transcriptional factor of LINC02532 and was shown to repress LINC02532 expression by negative transcriptional regulation. Conclusions Together, these findings show that LINC02532 promotes GC progression through epithelial–mesenchymal transition (EMT). Cross-talk between the FOXF2/LINC02532/SOX7 axis may provide a novel target for the treatment and prognostic prediction of GC.

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Circular RNA CDR1as Inhibits the Metastasis of Gastric Cancer through Targeting miR-876-5p/GNG7 Axis

Gastroenterology Research and Practice ◽

10.1155/2021/5583029 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jiajia Jiang ◽

Rong Li ◽

Junyi Wang ◽

Jie Hou ◽

Hui Qian ◽

...

Keyword(s):

Gastric Cancer ◽

Epithelial Mesenchymal Transition ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Luciferase Reporter Gene ◽

Mesenchymal Transition ◽

Underlying Mechanisms

Circular RNA CDR1as has been demonstrated to participate in various cancer progressions as miRNA sponges. The exact underlying mechanisms of CDR1as on gastric cancer (GC) metastasis remain unknown. Here, we found that CDR1as knockdown facilitated GC cell migration and invasion while its overexpression inhibited the migration and invasion abilities of GC cells in vitro and in vivo. Moreover, epithelial-mesenchymal transition- (EMT-) associated proteins and MMP2 and MMP9 were downregulated by CDR1as. Bioinformatics analysis combined with dual-luciferase reporter gene assays, western blot, RT-qPCR analysis, and functional rescue experiments demonstrated that CDR1as served as a miR-876-5p sponge and upregulated the target gene GNG7 expression to suppress GC metastasis. In summary, our findings indicate that CDR1as suppresses GC metastasis through the CDR1as/miR-876-5p/GNG7 axis.

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MiR-200b Suppresses Gastric Cancer Cell Migration and Invasion by Inhibiting NRG1 through ERBB2/ERBB3 Signaling

Journal of Oncology ◽

10.1155/2021/4470778 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Tonglei Xu ◽

Fangliang Xie ◽

Dazhou Xu ◽

Weidong Xu ◽

Xuming Ge ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Epithelial Mesenchymal Transition ◽

Inhibitory Effect ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Neuregulin 1 ◽

Mesenchymal Transition ◽

Cell Migration And Invasion ◽

Erbb3 Signaling

Purpose. Accumulating evidence indicates that miRNAs (miRs) play crucial roles in the modulation of tumors development. However, the accurately mechanisms have not been entirely clarified. In this study, we aimed to explore the role of miR-200b in the development of gastric cancer (GC). Methods. Western blot and RT-PCR were applied to detect epithelial-mesenchymal transition (EMT) marker expression and mRNA expression. Transwell assay was used for measuring the metastasis and invasiveness of GC cells. TargetScan system, luciferase reporter assay, and rescue experiments were applied for validating the direct target of miR-200b. Results. MiR-200b was prominently decreased in GC tissues and cells, and its downregulation was an indicator of poor prognosis of GC patients. Reexpression of miR-200b suppressed EMT along with GC cell migration and invasion. Neuregulin 1 (NRG1) was validated as the target of miR-200b, and it rescued miR-200b inhibitory effect on GC progression. In GC tissues, the correlation of miR-200b with NRG1 was inverse. Conclusion. MiR-200b suppressed EMT-related migration and invasion of GC through the ERBB2/ERBB3 signaling pathway via targeting NRG1.

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The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer

Cellular Oncology ◽

10.1007/s13402-020-00553-1 ◽

2020 ◽

Vol 43 (6) ◽

pp. 1017-1033 ◽

Cited By ~ 1

Author(s):

Yizhi Xiao ◽

Side Liu ◽

Jiaying Li ◽

Weiyu Dai ◽

Weimei Tang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Epithelial Mesenchymal Transition ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Aberrant Expression ◽

Mesenchymal Transition

Abstract Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman’s correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells.

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Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo

Drug Design Development and Therapy ◽

10.2147/dddt.s89805 ◽

2015 ◽

pp. 5579 ◽

Cited By ~ 7

Author(s):

Siyu Chen ◽

Lian Zhang ◽

Sungkyoung Kim ◽

Wenping Ding ◽

Yingying Tong ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Migration And Invasion ◽

Arsenic Sulfide ◽

Cell Migration And Invasion

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LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target

Oncogene ◽

10.1038/s41388-021-01656-1 ◽

2021 ◽

Author(s):

Xi Kang ◽

Weilin Li ◽

Weixin Liu ◽

Han Liang ◽

Jingyu Deng ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Peritoneal Metastasis ◽

Therapeutic Target ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Cell Migration And Invasion

AbstractPeritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.

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Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919874651 ◽

2019 ◽

Vol 11 ◽

pp. 175883591987465 ◽

Cited By ~ 11

Author(s):

Lin-Lin Wang ◽

Lei Zhang ◽

Xiao-Feng Cui

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Tumor Growth ◽

Noncoding Rna ◽

Mtor Pathway ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Tumor Growth And Metastasis

Background: Accumulating evidence has highlighted the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis of gastric cancer (GC), which is the most common gastrointestinal malignancy. The present study aimed to identify the capacity of lncRNA LINC01419 (LINC01419) in GC progression, with the potential mechanism explored. Methods: Highly expressed lncRNAs were identified by in silico analysis, with the LINC01419 expression in GC tissues measured using reverse transcription-quantitative PCR (RT-qPCR). The GC cells were subsequently transfected with siRNA against LINC01419 or Rapamycin (the inhibitor of the mTOR pathway), or both, in order to measure cell migration and invasion in vitro as well as tumor growth and metastasis in vivo. Moreover, the expression of PI3K/Akt1/mTOR pathway-associated factors was determined. Results: LINC01419, highly expressed in GC samples of the Gene Expression Omnibus database, was observed to be markedly upregulated in GC tissues. Moreover, LINC01419 silencing, or PI3K/Akt1/mTOR pathway inhibition, exhibited an inhibitory role in GC cell migration and invasion in vitro, coupled with promoted cell autophagy in vitro, and inhibited tumor growth and metastasis in vivo. It was also revealed that LINC01419 silencing blocked the PI3K/Akt1/mTOR pathway, as proved by decreased extents of Akt1 and mTOR phosphorylation. Conclusions: In conclusion, LINC01419 inhibition may suppress GC cell invasion and migration, and promote autophagy via inhibition of the PI3K/Akt1/mTOR pathway. This provides significant theoretical basis and possibilities for further elucidation of the molecular mechanism of GC and finding new molecular-targeted therapeutic regimens.

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MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2

Cellular Physiology and Biochemistry ◽

10.1159/000490839 ◽

2018 ◽

Vol 47 (4) ◽

pp. 1465-1481 ◽

Cited By ~ 21

Author(s):

Yu He ◽

Yugang Ge ◽

Mingkun Jiang ◽

Jundong Zhou ◽

Dakui Luo ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathways ◽

Cell Counting ◽

Erk Signaling ◽

Luciferase Reporter ◽

Population Doubling ◽

Migration And Invasion ◽

Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is one of the most prevalent digestive malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes, including oncogenesis, and miR-592 itself participates in many malignancies; however, its role in GC remains unknown. In this study, we investigated the expression and molecular mechanisms of miR-592 in GC. Methods: Quantitative real-time PCR and immunohistochemistry were performed to determine the expression of miR-592 and its putative targets in human tissues and cell lines. Proliferation, migration, and invasion were evaluated by Cell Counting Kit-8, population doubling time, colony formation, Transwell, and wound-healing assays in transfected GC cells in vitro. A dual-luciferase reporter assay was used to determine whether miR-592 could directly bind its target. A tumorigenesis assay was used to study whether miR-592 affected GC growth in vivo. Proteins involved in signaling pathways and the epithelial–mesenchymal transition (EMT) were detected with western blot. Results: The ectopic expression of miR-592 promoted GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially counteracted the effects of miR-592. miR-592 induced the EMT and promoted its progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2. Conclusions: Overexpression of miR-592 promotes GC proliferation, migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target for GC.

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ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer

Biomolecules ◽

10.3390/biom11040561 ◽

2021 ◽

Vol 11 (4) ◽

pp. 561

Author(s):

Yingming Jiang ◽

Xihu Yu ◽

Yandong Zhao ◽

Jintuan Huang ◽

Tuoyang Li ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Cell Migration ◽

Calcium Binding ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Human Gastric Cancer ◽

Cell Migration And Invasion ◽

Qrt Pcr

A Disintegrin and Metalloproteinase with Thrombospondin motifs 19 (ADAMTS19) has been reported to participate in the pathogenesis of solid cancers. However, its role in gastric cancer (GC) remains undocumented. Using immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) on GC tissues and adjacent normal tissues, we found that ADAMTS19 was downregulated in GC tissues (IHC: p < 0.001; qRT-PCR: p = 0.017). Further investigation revealed that ADAMTS19 correlated with distant metastasis (p = 0.008) and perineural invasion (p = 0.018) and that patients with low ADAMTS19 had worse overall survival (p = 0.021). Gain- and loss-of-function assays showed that ADAMTS19 suppressed cell migration and invasion in vitro. Using bioinformatics analysis and co-immunoprecipitation, immunofluorescence, and dual-luciferase reporter gene assays, we confirmed that ADAMTS19 binds with cytoplasm P65, decreasing the nucleus phosphorylation of P65, a crucial transcription factor in the nuclear factor kappa-B (NF-κB) pathway, thereby downregulating S100 calcium-binding protein A16 (S100A16) expression. S100A16 acted as the downstream of ADAMTS19, reversing the suppression of cell migration and invasion by ADAMTS19 in vitro. A combination of ADAMTS19 and S100A16 expression provided the optimal prognostic indicator for GC. Patients with ADAMTS19high-S100A16low had better overall survival than ADAMTS19low-S100A16high patients (p = 0.006). These results suggest that ADAMTS19 suppresses cell migration and invasion by targeting S100A16 via the NF-κB pathway and that ADAMTS19 and S100A16 are potential metastasis and survival biomarkers for GC.

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Visfatin facilitates gastric cancer malignancy by targeting snai1 via the NF-κB signaling

Human & Experimental Toxicology ◽

10.1177/09603271211006168 ◽

2021 ◽

pp. 096032712110061

Author(s):

D Cao ◽

L Chu ◽

Z Xu ◽

J Gong ◽

R Deng ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Western Blot ◽

Blot Analysis ◽

Western Blot Analysis ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Cell Migration And Invasion ◽

Protein Levels

Background: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. Methods: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. Results: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. Conclusion: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.

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Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽

10.3390/molecules26082204 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2204

Author(s):

Meng-Die Yang ◽

Yang Sun ◽

Wen-Jun Zhou ◽

Xiao-Zheng Xie ◽

Qian-Mei Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Tumor Growth ◽

Cell Viability ◽

Synergistic Effects ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

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