scholarly journals Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Jian Li ◽  
Danli Ye ◽  
Peng Shen ◽  
Xiaorong Liu ◽  
Peirong Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Mtor Signaling ◽  
Tumour Suppressor ◽  
Mtor Signaling Pathway

Abstract Background: The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms’ tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated. Methods: WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway which was regulated by WTX during GC progression was searched by KEGG pathway analysis. The miRNA which monitored WTX expression was screened by miRNA microarray. After verified the pathway and miRNA both in vitro and in vivo, the relationship of miRNA, WTX and the downstream pathway were analyzed by Western blot, immunohistochemistry, RT-PCR, Co-immunoprecipitation (Co-IP), and luciferase analyses.Results: The results showed that WTX serves as a tumour suppressor gene in GC. The loss of WTX which is associated with the aggressiveness of GC by promoting GC cell proliferation in vitro and high metastasis in vivo. Furthermore, WTX expression was positively correlated with the overall survival of GC patients. Microarray assays, bioinformatics analysis, and verification experiments showed that WTX loss activates the PI3K/AKT/mTOR pathway and promotes GC cell proliferation and invasion. And the aberrant miR-20a-5p upregulation contributes to WTX loss in GC, which stimulates PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway and promoted GC progression.Conclusions: The results of the present study elucidated the mechanism of GC progression, which is at least partially caused by aberrant miR-20a-5p upregulation leading to the inhibition of WTX expression and PI3K/AKT/mTOR signaling pathway activation. These findings provide a comprehensive understanding of the action of the miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

scholarly journals Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Jian Li ◽  
Danli Ye ◽  
Peng Shen ◽  
Xiaorong Liu ◽  
Peirong Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Mtor Signaling ◽  
Tumour Suppressor ◽  
Mtor Signaling Pathway

Abstract Background The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms’ tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated. Methods WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway which was regulated by WTX during GC progression was searched by KEGG pathway analysis. The miRNA which monitored WTX expression was screened by miRNA microarray. After verified the pathway and miRNA both in vitro and in vivo, the relationship of miRNA, WTX and the downstream pathway were analyzed by Western blot, immunohistochemistry, RT-PCR, Co-immunoprecipitation (Co-IP), and luciferase analyses. Results The results showed that WTX serves as a tumour suppressor gene in GC. The loss of WTX which is associated with the aggressiveness of GC by promoting GC cell proliferation in vitro and high metastasis in vivo. Furthermore, WTX expression was positively correlated with the overall survival of GC patients. Microarray assays, bioinformatics analysis, and verification experiments showed that WTX loss activates the PI3K/AKT/mTOR pathway and promotes GC cell proliferation and invasion. And the aberrant miR-20a-5p upregulation contributes to WTX loss in GC, which stimulates PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway and promoted GC progression. Conclusions The results of the present study elucidated the mechanism of GC progression, which is at least partially caused by aberrant miR-20a-5p upregulation leading to the inhibition of WTX expression and PI3K/AKT/mTOR signaling pathway activation. These findings provide a comprehensive understanding of the action of the miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

scholarly journals Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 20 ◽  
pp. 153303382199007
Author(s):  
Wenlin Liu ◽  
Jiandong Zhan ◽  
Rong Zhong ◽  
Rui Li ◽  
Xiaoli Sheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Laryngeal Cancer ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Lncrna Gas5

Background: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. Methods: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. Results: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. Conclusion: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

scholarly journals ANXA1 Induces Oxaliplatin Resistance of Gastric Cancer through Autophagy by Targeting PI3K/AKT/mTOR

2021 ◽  
Author(s):  
Jun Ren ◽  
Qing Zhi Hu ◽  
Ming Geng Niu ◽  
Jie Xia ◽  
Xing Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Mtor Signaling ◽  
Gene Set Enrichment Analysis ◽  
Rna Seq ◽  
Mtor Signaling Pathway

Abstract Background: Resistance to oxaliplatin (OXA) is a major cause of recurrence in gastric cancer (GC) patients. ANXA1 has been found to participate in the regulation of diverse cellular functions in a variety of cell types including anti-inflammatory processes. We aimed to investigate the role of ANXA1 in autophagy and chemoresistance of GC cells. Methods: To identify the genes that regulate oxaliplatin resistance, we used RNA-seq to profile gene expression within oxaliplatin resistant GC and parental cells. Immunohistochemical and RT-qPCR was performed to detect ANXA1 expression in tissues of 2 cohorts of GC patients who received OXA-based chemotherapy. The chemoresistant effects of ANXA1 were assessed by cell viability, apoptosis, and autophagy assays. The effects of ANXA1 on autophagy were assessed by mRFP-GFP-LC3 and western blot. Gene set enrichment analysis (GSEA) and western blot was performed to detect the activity of PI3K/AKT/mTOR signaling under the regulation of ANXA1.Results: Based on RNA-seq profiling, ANXA1 was selected as a candidate that was upregulated in oxaliplatin resistant GC cells. Furthermore, we discovered that ANXA1 is upregulated in chemo-resistant GC tissues. Knockdown of ANXA1, via inhibiting autophagy, enhanced the sensitivity of OXA-resistant GC cells to OXA in vitro and in vivo. Mechanically, we identified that PI3K/AKT/mTOR signaling pathway was activated in the ANXA1 stably knockdown AGS/OXA cells, which leads to the down-regulation of autophagy.Conclusions: ANXA1 functions as a chemoresistant gene in GC cells by targeting the PI3K/AKT/mTOR signaling pathway and might be a prognostic predictor for GC patients who receive OXA-based chemotherapy.

scholarly journals Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

2020 ◽  
Author(s):  
Jian Li ◽  
Danli Ye ◽  
Peng Shen ◽  
Xiaorong Liu ◽  
Peirong Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Wilms Tumor ◽  
Mtor Signaling ◽  
Luciferase Assay ◽  
Mtor Signaling Pathway ◽  
Pathway Analyses

Abstract Background: The X-linked gene WTX (also called AMER1), has been reported to act as a tumor suppress gene in Wilms tumor. Our previous study reported that WTX expression was significantly reduced in gastric cancer (GC), but the function and mechanism of WTX loss had not been fully elucidated yet. Methods: WTX/miR-20a-5p expression was analyzed in paraffin-embedded archived GC tissues and validated in public databases. KEGG pathway analyses were performed to explore the mechanism of WTX in GC progression. The role of WTX/miR-20a-5p in cell growth, migration, invasion and angiogenesis was investigated in vitro and in vivo. Western blot, immunohistochemistry, RT-PCR, luciferase assay, and Co-immunoprecipitation (Co-IP) were used to detect the regulation of WTX and PI3K/AKT/mTOR signaling by miR-20a-5p.Results: We revealed that WTX served as a tumor suppressor whose loss associated with the aggressive feature of GC by showing hyperproliferation in vitro and high metastasis phenotype in vivo. And WTX expression level was positively correlated with the overall survival of GC patients. Microarray, bioinformatics analysis, and verification experiments showed that WTX loss activated PI3K/AKT/mTOR pathway, and promoted the proliferation and invasion of GC cells. We also discovered that the miR-20a-5P aberrant upregulation was one of the reasons inducing WTX loss in GC which stimulated PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway, thus promoted GC progression.Conclusions: This study unveiled the mechanism of GC progression which was, at least partially, caused by miR-20a-5p aberrant upregulation which inhibited WTX expression and thus activate PI3K/AKT/mTOR signaling pathway. It provided a comprehensive understanding of the action of miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

scholarly journals Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hong-Bo Li ◽  
Jun-Kai Chen ◽  
Ze-Xin Su ◽  
Qing-Lin Jin ◽  
Li-Wen Deng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mtor Signaling ◽  
Osteosarcoma Cell ◽  
Mtor Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Related Proteins

Abstract Background Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. Methods CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. Results Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. Conclusions In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

MO243STUDY ON THE EFFECT AND MECHANISM OF NOVEL REGULATORY T CELL (CD4+CD126LOWFOXP3+ TREG) IMMUNOTHERAPY IN LUPUS NEPHRITIS*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Zhenjian Xu ◽  
Junzhe Chen ◽  
Anping Xu
Keyword(s):  
T Cell ◽  
Lupus Nephritis ◽  
Signaling Pathway ◽  
B Lymphocytes ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Differentiation ◽  
Inflammatory State

Abstract Background and Aims Our previous study found a new regulatory T cell subpopulation, CD4+CD126lowFoxp3+ regulatory T cells (CD4+CD126lowFoxp3+ Treg). This cell can maintain a stable immune regulatory function in the inflammatory state. Through in vivo and in vitro experiments, we have confirmed that CD4+CD126lowFoxp3+ Treg has an immunotherapeutic effect on T cell-mediated mouse models of autoimmune diseases such as colitis and collagen-induced arthritis (CIA). Further experimental studies showed that CD4+CD126lowFoxp3+ Treg could reduce the kidney injury caused by autoantibodies and prolong the survival time of lupus mice. However, the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in lupus nephritis is not clear. The purpose of this study was to explore the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in mice with lupus nephritis. Method In vitro experiments CD4+CD126lowFoxp3+ Treg or CD4+CD126lowFoxp3+ Treg pretreated with PD-1 inhibitor were co-cultured with T or B lymphocytes of lupus mice under different in vitro culture condition. The expression levels of Akt and mTOR of Treg in each group were measured under immunoinflammatory conditions. To observe the effects and differences of Treg groups on the activation, proliferation and differentiation of T or B cells and other immunomodulatory effects. In vivo experiments CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) and CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) pretreated with PD-1 inhibitor and PBS were injected into NZM2328 lupus mice, respectively. After cell injection, urine protein was measured weekly. Autoantibody expression in lupus mice was measured every two weeks. The effects of Treg on the proliferation and differentiation of T/B cells in lupus mice were observed. The therapeutic effects of Treg on lupus mice were observed. Results Compared with CD4+CD126lowFoxp3+ Treg, the expression of Akt and mTOR increases in PD-1 inhibitors pretreatment cells. The activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vitro, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-mTOR signaling pathway through PD-1 in in vitro. Compared with CD4+CD126lowFoxp3+ Treg, the activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vivo. And its therapeutic effect on lupus mice was ineffective, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-MTOR signaling pathway through PD-1 in vivo. Conclusion CD4+CD126lowFoxp3+ Treg may inhibit the Akt-mTOR signaling pathway by expressing PD-1, and maintain stable immunomodulatory function in the inflammatory state, thus producing immunotherapeutic effect on lupus nephritis mice.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF-α Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K-Akt-mTOR Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Guangtao Han ◽  
Yubiao Zhang ◽  
Haohuan Li
Keyword(s):  
Signaling Pathway ◽  
Combination Treatment ◽  
Inflammatory Cytokine ◽  
Combined Treatment ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Tnf Α

Osteoarthritis (OA) is a chronic joint disease characterized by cholesterol accumulation in chondrocytes, cartilage degeneration, as well as extracellular matrix (ECM) destruction, and joint dysfunction. Curcumin, a chemical that can reduce cholesterol levels in OA patients, also can inhibit the progression of OA. However, a high concentration of curcumin may also trigger apoptosis in normal chondrocytes. Besides curcumin, probucol that is found can also effectively decrease the cholesterol level in OA patients. Considering that high cholesterol is a risk factor of OA, it is speculated that the combination treatment of curcumin and probucol may be effective in the prevention of OA. To investigate the possible effects of such two chemicals on OA pathophysiology, chondrocyte apoptosis and autophagy behavior under inflammatory cytokine stress were studied, and specifically, the PI3K-Akt-mTOR signaling pathway was studied. Methods. Cell proliferation, colony formation, and EdU assay were performed to identify the cytotoxicity of curcumin and probucol on chondrocytes. Transwell assay was conducted to evaluate chondrocyte migration under TNF-α inflammation stress. Immunofluorescence, JC-1, flow cytometry, RT-PCR, and western blot were used to investigate the signal variations related to autophagy and apoptosis in chondrocytes and cartilage. A histological study was carried out on OA cartilage. Glycosaminoglycan (GAG) release was determined to evaluate the ECM degradation under stress. Results. Compared with a single intervention with curcumin or probucol, a combined treatment of these two chemicals is more effective in terms of protecting chondrocytes from stress injury induced by inflammatory cytokines. The promoted protection may be attributed to the inhibition of apoptosis and the blockage of the autophagy-related PI3K/Akt/mTOR pathway. Such results were also verified in vitro by immunofluorescence staining of OA chondrocytes and in vivo by immunohistochemistry staining of cartilage. Besides, in vivo studies also showed that when applied in combination, curcumin and probucol could block the PI3K-AKT-mTOR signaling pathway; promote COL-II expression; suppress P62, MMP-3, and MMP-13 expression; and inhibit TNF-α-stimulated cartilage degradation. Moreover, the combined medication could help reduce the release of ECM GAGs in OA cartilage and alleviate the severity of OA. Conclusion. A combined treatment of curcumin and probucol could be used to protect chondrocytes from inflammatory cytokine stress via inhibition of the autophagy-related PI3K/Akt/mTOR pathway both in vitro and in vivo, which might be of potential pharmaceutical value for OA prevention and therapy.

scholarly journals MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Ags Cells

Abstract MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.

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