Dataset Information

MiR-502-5p affects gastric cancer progression by targeting PD-L1.

ABSTRACT: Background:Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer. Methods:Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot. Results:The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels. Conclusions:These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.

SUBMITTER: You W

PROVIDER: S-EPMC7429713 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-502-5p affects gastric cancer progression by targeting PD-L1.

You Wendao W Liu Xiaoyu X Yu Yang Y Chen Chen C Xiong Yujia Y Liu Yiting Y Sun Yibin Y Tan Chenhuan C Zhang Hanshuo H Wang Yadong Y Li Rui R

Cancer cell international 20200815

<h4>Background</h4>Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer.<h4>Methods</h4>Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by tran ...[more]

PMID: 32821248

Similar Datasets

Project description:BackgroundColorectal cancer (CRC) poses a heavy threat to human health owing to its high incidence and mortality. Circular RNAs (circRNAs) were investigated to participate in the progression of CRC, whereas there was no revenant data on the CRC process regulated by hsa_circ_0000231. This study aimed to explore the effects of hsa_circ_0000231 on CRC progression and underneath regulatory mechanism.MethodsThe expression levels of hsa_circ_0000231, miR-502-5p, and Myosin VI (MYO6) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). Western blot was employed to determine the protein expression levels of MYO6 and proliferating cell nuclear antigen (PCNA). The effects of hsa_circ_0000231 on cell proliferation, apoptosis, migration, and invasive in CRC were determined by cell counting kit-8 proliferation (CCK-8) and colony formation assays, flow cytometry analysis, wound-healing assay, and transwell invasion assay, respectively. Glucose uptake and lactate production were severally illustrated by glucose assay kit and lactate assay kit. The relationship between miR-502-5p and hsa_circ_0000231 or MYO6 was predicted by circular RNA interactome or targetScan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo tumor formation assay was carried out to determine the effects of hsa_circ_0000231 knockdown on tumor growth in vivo.ResultsHsa_circ_0000231 expression was dramatically upregulated while miR-502-5p was obviously downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0000231 knockdown repressed the expression levels of MYO6 and PCNA protein. Functionally, hsa_circ_0000231 knockdown repressed cell glycolysis, proliferation, migration and invasion, and induced cell apoptosis, whereas these effects were decreased by miR-502-5p inhibitor. Mechanistically, hsa_circ_0000231 acted as a sponge of miR-502-5p and miR-502-5p bound to MYO6. Furthermore, hsa_circ_0000231 knockdown decreased tumor volume and weight of CRC in vivo.ConclusionHsa_circ_0000231 knockdown inhibited CRC progression and glycolysis by downregulating MYO6 expression through sponging miR-502-5p, which might provide a theoretical basis in further studying circ_0000231-directed therapy in CRC.

Project description:BackgroundTargeted drugs are not quite effective for prolonging the survival of patients with gastric cancer due to off-target effects as well as tumor immune escape mechanisms. Circular RNAs widely exist in tumor regions as biomarkers and can be developed as effective drug targets.MethodsWestern blot, QRT-PCR, fluorescence in situ hybridization, and flow cytometry were used to investigate the function of hsa_circ_0136666 in promoting the proliferation of gastric cancer cells. Tissue immunofluorescence, enzyme-linked immunosorbent assay (ELISA), as well as flow cytometric analysis, was conducted to explore the process of tumor immune evasion in tumor-bearing mice. The differences of circRNA expression in clinical samples were analyzed through tissue microarray FISH. The effect of siRNA on improving the efficacy of anti-PDL1 drugs and suppressing the immune microenvironment was evaluated by the coadministration model.ResultsWe demonstrated that hsa_circ_0136666 was widely and highly expressed in gastric cancer tissues and cells. Functionally, hsa_circ_0136666 promoted gastric cancer tumor proliferation and tumor microenvironment formation, leading to tumorigenesis immune escape, and this effect was dependent on CD8 + T cells. Mechanistically, we confirmed that hsa_circ_0136666 competitively upregulated PRKDC expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting phosphorylation of PD-L1 to preventing its degradation, driving PD-L1 aggregation and suppressing immune function, thereby impairing cancer immune responses. In terms of application, we found that LNP-siRNA effectively improved anti-PDL1 drug efficacy and inhibited immune escape.ConclusionOur results reveal an oncogenic role played by hsa_circ_0136666 in gastric cancer, driving PD-L1 phosphorylation via the miR-375/PRKDC signaling axis, prompting immune escape. This work proposes a completely new pathogenic mechanism of gastric cancer, uncovers a novel role for hsa_circ_0136666 as an immune target, and provides a rationale for enhancing the efficacy of anti-PD-L1 therapy for gastric cancer.

Dataset Information

MiR-502-5p affects gastric cancer progression by targeting PD-L1.

Publications

miR-502-5p affects gastric cancer progression by targeting PD-L1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets