scholarly journals 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

2019 ◽  
Vol 11 ◽  
pp. 175883591987465 ◽  
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.

scholarly journals 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 ◽  
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.

scholarly journals Overexpression of long noncoding RNA GAS5 suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway

2019 ◽  
Author(s):  
Shuaijun Dong ◽  
Xiefu Zhang ◽  
Dechun Liu
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Mtor Pathway ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Non Coding Rnas ◽  
Development Of Gastric Cancer

AbstractLong non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. LncRNA GAS5 (GAS5) is identified tumor suppressor involved in several cancers. However, the roles of GAS5 and the mechanisms responsible for its functions in gastric cancer (GC) have not been well undocumented. Herein, the decreased GAS5 and increased miRNA-106a-5p levels were observed in GC and cell lines. GAS5 expression level was significantly inversely correlated with miRNA-106a-5p level in GC tissues. Moreover, luciferase reporter and qRT-PCR assays showed that GAS5 bound to miRNA-106a-5p and negatively regulated its expression in GC cells. Functional experiments showed that GAS5 overexpression suppressed GC cell proliferation, migration, and invasion capabilities and promoted apoptosis, while miRNA-106a-5p overexpression inversed the functional effects induced by GAS5 overexpression. In vivo, GAS5 overexpression inhibited tumor growth by negatively regulating miRNA-106a-5p expression. Mechanistic investigations revealed that GAS5 overexpression inactivating the Akt/mToR pathway by suppressing miRNA-106a-5p expression in vitro and in vivo. Taken together, our findings conclude the GAS5 overexpression suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway.

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

2015 ◽  
pp. 5579 ◽  
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

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

Oncogene ◽  
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.

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

2021 ◽  
Author(s):  
Cheng Zhang ◽  
Chun-Dong Zhang ◽  
Jun-Peng Pei ◽  
Yong-Zhi Li ◽  
Maimaititusun Yusupu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcriptional Regulation ◽  
Cell Migration ◽  
Mrna Stability ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

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.

scholarly journals BCAT1 Activates PI3K/AKT/mTOR Pathway and Contributes to the Angiogenesis and Tumorigenicity of Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiong Shu ◽  
Pan-Pan Zhan ◽  
Li-Xin Sun ◽  
Long Yu ◽  
Jun Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Western Blotting ◽  
Mtor Pathway ◽  
Clinical Samples ◽  
Xenograft Models ◽  
Cell Phenotypes

BackgroundFocusing on antiangiogenesis may provide promising choices for treatment of gastric cancer (GC). This study aimed to investigate the mechanistic role of BCAT1 in the pathogenesis of GC, particularly in angiogenesis.MethodsBioinformatics and clinical samples analysis were used to investigate the expression and potential mechanism of BCAT1 in GC. BGC823 cells with BCAT1 overexpression or silencing were induced by lentiviral transduction. Cell phenotypes and angiogenesis were evaluated. The relevant proteins were quantized by Western blotting, immunohistochemistry, or immunofluorescence. Xenograft models were constructed to confirm the role of BCAT1 in vivo.ResultsBCAT1 was overexpressed in GC patients and associated with lower survival. BCAT1 expression was correlated with proliferation-, invasion-, or angiogenesis-related markers expression and pathways. Silencing BCAT1 expression suppressed cell viability, colony formation, cycle progression, invasion, and angiogenesis of BGC823 cells, as well as the tumor growth of xenograft models, whereas overexpressing BCAT1 had the opposite results both in vitro and in vivo. Bioinformatics analysis and Western blotting demonstrated that BCAT1 activated the PI3K/AKT/mTOR pathway. The addition of LY294002 reversed the tumor growth induced by BCAT1 overexpression, further verifying this mechanism.ConclusionBCAT1 might act as an oncogene by facilitating proliferation, invasion, and angiogenesis through activation of the PI3K/AKT/mTOR pathway. This finding could aid the optimization of antiangiogenesis strategies.

scholarly journals LINC00319 acts as a microRNA-335–5p sponge to accelerate tumor growth and metastasis in gastric cancer by upregulating ADCY3

2020 ◽  
Vol 318 (1) ◽  
pp. G10-G22
Author(s):  
Jun Zou ◽  
Kun Wu ◽  
Chao Lin ◽  
Zhi-Gang Jie
Keyword(s):  
Gastric Cancer ◽  
Adenylate Cyclase ◽  
Tumor Growth ◽  
Micro Rna ◽  
In Vivo Experiments ◽  
Tumorigenesis And Progression ◽  
Tumor Growth And Metastasis ◽  
And Migration

Gastric cancer (GC) is one of the most common cancers in the world and remains a heavy burden of health worldwide. Adenylate cyclase 3 ( ADCY3) is a widely expressed membrane-associated protein in human tissues and has been identified to be a new molecular target of GC. Long noncoding RNAs have a substantial influence on tumorigenesis and progression of tumors by binding to microRNAs. Therefore, this study is to clarify the mechanism by which LINC00319 sponges micro RNA-335–5p ( miR-335–5p) to influence the development of GC. Initially, microarray analysis identified GC-related differentially expressed LINC00319 and ADCY3 for this study. The interaction was confirmed that LINC00319 interacted with miR-335–5p to regulate ADCY3. Next, SGC-7901 cells presenting with the lowest LINC00319 expression and the highest miR-335–5p expression were transfected with LINC00319, miR-335–5p inhibitor, or ADCY3 vector to examine their roles in growth and metastasis of GC cells, which was further ascertained by in vivo experiments. LINC00319 was upregulated and miR-335–5p was downregulated in GC cells. LINC00319 overexpression, miR-335–5p inhibitor, or ADCY3 overexpression was shown to significantly elevate the expression of cyclin-dependent kinase 4 and metastasis associated 1, decrease that of growth arrest-specific 1, and promote tumor growth and metastasis by increasing proliferation and migration and reducing cell apoptosis. Importantly, it was found that overexpressed miR-335–5p exerted its tumor suppressive role in GC through downregulating ADCY3. Collectively, LINC00319 expedited growth and metastasis of GC by upregulating miR-335–5p-mediated ADCY3. NEW & NOTEWORTHY This study is carried out based on in vivo and in vitro studies in mice and gastric cancer (GC) cells with the aim of clarifying the role of LINC00319 on GC growth and metastasis, which associated with micro RNA-335–5p-mediated adenylate cyclase 3. Altogether, we identified LINC00319 to be a potential therapy to treat GC.

scholarly journals Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Tao Chen ◽  
Fu-Kuan Zhong
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

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