Knockdown of PD-L1 in Human Gastric Cancer Cells Inhibits Tumor Progression and Improves the Cytotoxic Sensitivity to CIK Therapy

Background/Abstract: PD-L1 has been an important target of cancer immunotherapy. We have showed that in human gastric cancer tissues, over-expression of PD-L1 was significantly associated with cancer progression and patients’ postoperative prognoses. However, as of now, how PD-L1 regulates the biological function of gastric cancer cells still remains elusive. Methods: We constructed the stable PD-L1 knockdown expression gastric cancer cell lines by using RNAi method, and further investigated the changes of biological functions including cell viability, migration, invasion, cell cycle, apoptosis, tumorigenicity in vivo, and the cytotoxic sensitivity to CIK therapy, in contrast to the control cells. Results: In the current study, we demonstrated that the knockdown of PD-L1 expression in human gastric cancer cells could significantly suppress the cell proliferation, migration, invasion, apoptosis, cell cycle, tumorigenicity in vivo and the cytotoxic sensitivity to CIK therapy. Conclusion: Our results indicate that PD-L1 contributes towards transformation and progression of human gastric cancer cells, and its intervention could prove to be an important therapeutic strategy against gastric cancer.

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NSD1 stimulated survival and migration of gastric cancer cells through WNT10B

10.31083/jomh.2021.047 ◽

2021 ◽

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Progression ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Expression Levels ◽

Gastric Cancer Cell Lines ◽

And Migration ◽

Cancer Tissues

Background and objective: To assess the expression of Nuclear receptor binding SET domain protein 1 (NSD1) in human gastric cancer tissues and cells and investigate its possible role in gastric cancer. Methods: TCGA database was used to assess the expression levels of NSD1 in human gastric cancer tissues. Immunoblot assays were performed to detect NSD1 expression levels in gastric cancer cell lines. MTT and colony formation assays were conduced to detect its role in the survival of gastric cancer cells. Wound closure and transwell were performed to investigate the effects of NSD1 on the motility of gastric cancer cells. Immunoblot assays were also conducted to conﬁrm its effects on WNT10B/β-catenin pathway. Results: We found the high expression levels of NSD1 in human gastric cancer tissues and cell lines. NSD1 depletion suppressed the survival and motility of gastric cancer cells. Additionally, we revealed NSD1 activated the WNT10B/β-catenin pathway, therefore promoted gastric cancer progression. Conclusion: We revealed the high NSD1 expression in gastric cancer tissues and cells, and thought NSD1 could serve as a promising gastric cancer target.

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EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22

Biological Chemistry ◽

10.1515/hsz-2015-0279 ◽

2016 ◽

Vol 0 (0) ◽

Author(s):

Min Yang ◽

Nan Jiang ◽

Qi-wei Cao ◽

Qing Sun

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Patient Survival ◽

Underlying Mechanism ◽

Gastric Cancer Cells ◽

Cancer Tissues

Abstract Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

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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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Expression of FOXA1 gene regulates the proliferation and invasion of human gastric cancer cells

Cellular and Molecular Biology ◽

10.14715/cmb/2021.67.2.25 ◽

2021 ◽

Vol 67 (2) ◽

pp. 161-165

Author(s):

Yun Dai ◽

Guangming Yang ◽

Lie Yang ◽

Li Jiang ◽

Guohua Zheng ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Invasion ◽

Therapeutic Potential ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Therapeutic Implications ◽

Induction Of Apoptosis ◽

Cancer Tissues

Forkhead box (FOX) transcription factors regulate the development of several human cancers. However, the role and therapeutic potential of FOXA1 in gastric cancer is still largely unexplored. The results showed a significant (P < 0.05) upregulation of FOXA1 in gastric cancer tissues and cell lines. Silencing of FOXA1 in gastric cells significantly (P < 0.05) decreased their viability through induction of apoptosis. The induction of apoptosis was associated with upregulation of Bax and downregulation of Bcl-2. Additionally, FOXA1 silencing caused activation of caspase-3 and 9 with no apparent effects on the expression of caspase-8 suggestive of intrinsic apoptosis. The transwell cell invasion revealed significant (P < 0.05) decline of cell invasion of gastric cancer cells upon FOXA1 silencing. The FOXA1 knockdown further inhibited the in vivo tumor growth suggestive of its therapeutic potential. Taken together, the findings of the present revealed that FOXA1 regulates the proliferation and development of gastric cancer and may exhibit therapeutic implications in gastric cancer treatment.

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Diosgenin inhibits the proliferation of gastric cancer cells via inducing mesoderm posterior 1 down-regulation-mediated alternative reading frame expression

Human & Experimental Toxicology ◽

10.1177/09603271211053292 ◽

2021 ◽

pp. 096032712110532

Author(s):

Lin Gu ◽

Hailun Zheng ◽

Rui Zhao ◽

Xiaojing Zhang ◽

Qizhi Wang

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Reading Frame ◽

Anti Cancer ◽

Cancer Tissues ◽

Alternative Reading

Introduction Whether and how mesoderm posterior 1 (MESP1) plays a role in the proliferation of gastric cancer cells remain unclear. Methods The expression of MESP1 was compared in 48 human gastric cancer tissues and adjacent normal tissues. Knockdown of MESP1 was performed to investigate the role of MESP1 in the proliferation and apoptosis of BGC-823 and MGC-803 gastric cancer cells. Knockdown of alternative reading frame (ARF) was performed to study the role of ARF in the inhibitory effect of MESP1 knockdown on cell proliferation in gastric cancer cells. Mouse subcutaneous xenograft tumor model bearing BGC-823 cells was used to investigate the role of MESP1 in the growth of gastric tumor in vivo. The effect of seven active ingredients from T. terrestris on MESP1 expression was tested. The anti-cancer effect of diosgenin was confirmed in gastric cancer cells. MESP1 dependence of the anti-cancer effect of diosgenin was confirmed by MESP1 knockdown. Results MESP1 was highly expressed in human gastric cancer tissues ( p < 0.05). MESP1 knockdown induced apoptosis and up-regulated the expression of ARF in gastric cancer cells ( p < 0.05). Knockdown of ARF attenuated the anti-cancer effect of MESP1 knockdown ( p < 0.05). In addition, MESP1 knockdown also suppressed tumor growth in vivo ( p < 0.05). Diosgenin inhibits both mRNA and protein expression of MESP1 ( p < 0.05). MESP1 knockdown attenuated the anti-cancer effect of diosgenin ( p < 0.05). Conclusions MESP1 promotes the proliferation of gastric cancer cells via inhibiting ARF expression. Diosgenin exerts anti-cancer effect through inhibiting MESP1 expression in gastric cancer cells.

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LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00275-8 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

An Yang ◽

Xin Liu ◽

Ping Liu ◽

Yunzhang Feng ◽

Hongbo Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Apoptosis ◽

Gastric Cancer Cell ◽

Gastric Cancer Cells ◽

Gastric Cancer Cell Lines ◽

Development Of Gastric Cancer

Abstract Background Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. Methods The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. Results UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. Conclusions UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

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Total saponins from Tupistra chinensis Baker inhibits growth of human gastric cancer cells in vitro and in vivo

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114323 ◽

2021 ◽

pp. 114323

Author(s):

Zhe Wang ◽

Jingwen Xu ◽

Yihai Wang ◽

Limin Xiang ◽

Xiangjiu He

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Gastric Cancer Cells

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miR-335-5p Suppresses Gastric Cancer Progression by Targeting MAPK10

10.21203/rs.3.rs-52496/v1 ◽

2020 ◽

Author(s):

Yi Gao ◽

Yanfeng Wang ◽

Xiaofei Wang ◽

Changan Zhao ◽

Fenghui Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Progression ◽

Target Gene ◽

Luciferase Reporter ◽

Gastric Cancer Cells ◽

Aberrant Expression ◽

Related Target

Abstract Background: In recent years, many microRNAs(miRNAs) involved in cancer progression. The aberrant expression of miR-335-5p in tumorigenesis has been demonstrated. The present study aimed to investigate the molecular mechanisms underlying miR-335-5p- regulated MAPK10 expression in human gastric cancer（GC）.Methods: The quantitative real-time PCR was used to study the level of miR-335-5p expression in gastric cancer cell lines and tissues. Subsequently, the MTT and cloning formation assays were used to detect cell proliferation, while transwell and wound-healing assays were used to identify invasion and migration of the gastric cancer cells. The correlation between the miR-335-5p and the cell cycle-related target gene mitogen‑activated protein kinase 10 (MAPK10) in gastric cancer was analyzed based on the website. In addition, the target gene of miR-335-5p was detected by luciferase reporter assay, qRT-PCR, and western blotting.Results: The miR-335-5p level was down-regulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited proliferation, migration of gastric cancer cells, and induced apoptosis. During the G1/S phase, miR-335-5p arrested the cycle of gastric cancer cells in vitro. The correlation between the miR-335-5p and the cell cycle-related target gene MAPK10 in GC was analyzed, MAPK10 was directly targeted by the miR-335-5p.Conclusion: These data suggested that miR-335-5p acts as a tumor suppressor, and go through the MAPK10 to inhibit the GC progression.

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Apelin Over-Expression Promotes Proliferation and Angiogenesis of Gastric Cancer Cells

10.21203/rs.3.rs-530677/v2 ◽

2021 ◽

Author(s):

Li-Jun Tian ◽

Hong-Zhi Liu ◽

Qiang Zhang ◽

Dian-Zhong Geng ◽

Jing Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Cyclin D1 ◽

Cancer Cells ◽

Signaling Pathway ◽

Cox Regression ◽

Gastric Cancer Cells ◽

Over Expression ◽

Normal Tissues

Abstract Background: Apelin is a recently identified endogenous ligand associated with proliferation and angiogenesis of several cancers. However, only few studies have reported on the functions and the role of apelin in gastric cancer (GC). Therefore, in the present study, we investigated the association and the mechanisms underlying Apelin expression and proliferation of GC cells both in vitro and in vivo.Methods: We enrolled 178 postoperative care GC patients to investigate clinicopathological and immunohistochemical factors associated with Apelin expression. The relationship between Survival of patients and apelin expression was evaluated using Kaplan-Meier method and Cox regression analyses. The expression of apelin mRNA and its proteins in GC tissues and cell lines were analyzed using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA. The role and mechanisms underlying regulation of Apelin expression in human GC cells were evaluated through several in vitro and in vivo experiments. Results: Apelin was over expressed in human GC cells, relative to adjacent normal tissues. The over expression of apelin was associated with vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) (P <0.05), worse pathological type (P <0.05), nerve invasion (P <0.05). In addition, expression of apelin strongly and positively correlated with that of vascular endothelial growth factor (VEGF). Over-expression of apelin promoted proliferation and invasion of MGC-803 cell via the ERK/Cyclin D1/MMP-9 signaling pathway. Apelin over-expression also promoted angiogenesis of GC cells, accelerating growth of subcutaneous xenograft of the cancer cells in vivo.Conclusions: Over-expression of apelin promotes proliferation and metastasis of GC cells via the ERK/Cyclin D1/MMP-9 signaling pathway and is associated with adverse events of the cancer. Consequently, apelin is a potential therapeutic target for human GC.

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