Role of microRNA 4717, its effects on programmed cell death protein-1 in hepatitis B infection, and interaction between PDCD1 and miR-4717

It is suggested that programmed cell death protein-1 (PD-1) is involved in hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma globally. This study was multi-aimed, that is, to investigate the role of microRNA (miR) 4717 and its target, PD-1 and to determine how the rs10204525 polymorphism in the 3′ untranslated region (3′UTR) of PD-1 affects its interaction with miR-4717. The expression levels of miR-4717 with various single-nucleotide polymorphisms were measured by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). A total of 54 tissue samples from HBV-infected individuals were collected, genotyped, and categorized into three groups; AA (n = 32), AG (n = 18), and GG (n = 4). The expression levels of gene PDCD1 and its corresponding PD-1 protein were significantly declined in the AA group as compared to AG and GG groups. There was a negative linear association between PDCD1 and miR-4717 in the tissue samples. HEPG2 cells transfected with an miR-4717 mimic or PD-1 small interfering (si)RNA exhibited significantly reduced expression levels of PDCD1 and PD-1, whereas cells transfected with an inhibitor of miR-4717 demonstrated greater expression levels of PDCD1 and PD-1 compared with the scramble control. In addition, cell viability and apoptosis were assessed in cells transfected with an miR-4717 mimic, PD-1 siRNA, or an miR-4717 inhibitor. Results revealed that treatment with the miR-4717 mimic or PD-1 siRNA enhanced viability of cells and reduced apoptosis. The results of this study suggest that rs10204525 polymorphism interferes with the interaction between PD-1 and miR-4717 and therefore induces apoptosis in liver cancer cells.

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Abstract 417: Role of programmed cell death protein-1 (PD-1)-targeted immunotherapy in hepatocellular carcinoma

10.1158/1538-7445.am2021-417 ◽

2021 ◽

Author(s):

Shaohua Li ◽

Jie Mei ◽

Qiaoxuan Wang ◽

Wei Wei ◽

Lianghe Lu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Death ◽

Programmed Cell Death ◽

Cell Death Protein ◽

Targeted Immunotherapy

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Up-regulation of MicroRNA-21 Mediates Isoflurane-induced Protection of Cardiomyocytes

Anesthesiology ◽

10.1097/aln.0000000000000567 ◽

2015 ◽

Vol 122 (4) ◽

pp. 795-805 ◽

Cited By ~ 29

Author(s):

Jessica M. Olson ◽

Yasheng Yan ◽

Xiaowen Bai ◽

Zhi-Dong Ge ◽

Mingyu Liang ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Messenger Rna ◽

Functional Role ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cell Death Protein

Abstract Background: Anesthetic cardioprotection reduces myocardial infarct size after ischemia–reperfusion injury. Currently, the role of microRNA in this process remains unknown. MicroRNAs are short, noncoding nucleotide sequences that negatively regulate gene expression through degradation or suppression of messenger RNA. In this study, the authors uncovered the functional role of microRNA-21 (miR-21) up-regulation after anesthetic exposure. Methods: MicroRNA and messenger RNA expression changes were analyzed by quantitative real-time polymerase chain reaction in cardiomyocytes after exposure to isoflurane. Lactate dehydrogenase release assay and propidium iodide staining were conducted after inhibition of miR-21. miR-21 target expression was analyzed by Western blot. The functional role of miR-21 was confirmed in vivo in both wild-type and miR-21 knockout mice. Results: Isoflurane induces an acute up-regulation of miR-21 in both in vivo and in vitro rat models (n = 6, 247.8 ± 27.5% and 258.5 ± 9.0%), which mediates protection to cardiomyocytes through down-regulation of programmed cell death protein 4 messenger RNA (n = 3, 82.0 ± 4.9% of control group). This protective effect was confirmed by knockdown of miR-21 and programmed cell death protein 4 in vitro. In addition, the protective effect of isoflurane was abolished in miR-21 knockout mice in vivo, with no significant decrease in infarct size compared with nonexposed controls (n = 8, 62.3 ± 4.6% and 56.2 ± 3.2%). Conclusions: The authors demonstrate for the first time that isoflurane mediates protection of cardiomyocytes against oxidative stress via an miR-21/programmed cell death protein 4 pathway. These results reveal a novel mechanism by which the damage done by ischemia/reperfusion injury may be decreased.

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The role of the programmed cell death protein-1/programmed death-ligand 1 pathway, regulatory T cells and T helper 17 cells in tumor immunity: a narrative review

Annals of Translational Medicine ◽

10.21037/atm-20-6719 ◽

2020 ◽

Vol 8 (22) ◽

pp. 1526-1526

Author(s):

Lanfang Zhang ◽

Mingjuan Zhang ◽

Jinxiu Xu ◽

Shan Li ◽

Yu Chen ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

Programmed Cell Death ◽

T Helper ◽

T Helper 17 ◽

T Helper 17 Cells ◽

Programmed Death Ligand 1 ◽

Programmed Death ◽

Cell Death Protein

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Prognostic role of programmed cell death protein 1 expression in surgically treated patients with upper tract urothelial carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.402 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 402-402

Author(s):

Nozomi Hayakawa ◽

Eiji Kikuchi ◽

Ryuichi Mizuno ◽

Keishiro Fukumoto ◽

Takeo Kosaka ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Protein Expression ◽

Urothelial Carcinoma ◽

Lymphovascular Invasion ◽

Upper Tract Urothelial Carcinoma ◽

Upper Tract ◽

Significant Difference ◽

Cell Death Protein

402 Background: Programmed cell death protein (PD-1) expressed on active T cells, and its ligand PD-L1 expressed on the surface of cancer cells, complementarily down-regulate T cell activation and are related to immune tolerance. A close association between PD-1 expression and poor prognosis has been reported in several cancers, however, in upper tract urothelial carcinoma (UTUC) the role of PD-1 expression on clinical outcome has not been investigated. Methods: The protein expression of PD-1 was evaluated by immunohistochemistry and the relationship with clinicopathological features was investigated in surgical specimens obtained from 100 patients who had been surgically treated for UTUC. At a magnification of 200x, PD-1 protein expression was estimated and the positive cells were graded as no (negative), moderate (1-10 cells), and strong ( > 10 cells). Results: Twenty-four patients (24.0%) had strong PD-1 staining, 32 patients (32.0%) had moderate PD-1 staining, and 44 patients (44.0%) had no PD-1 staining. PD-1 staining was associated with pathological T stage (p = 0.023), tumor grade (p = 0.005), and lymphovascular invasion (p = 0.033). Lymphovascular invasion (p < 0.001) and PD-1 staining (p = 0.02) were independent factors for predicting disease metastasis. The 5-year matastatic free survival rate in patients with strong PD-1 staining was 57.3 %, which was significantly lower than that with no PD-1 staining (87.3%, p=0.001) and that with moderate PD-1 staining (74.3%, p = 0.05). In a sub-group analysis of patients with ≥pT2 (N = 59), a significant difference in disease metastasis was observed between patients with strong PD-1 staining and no PD-1 staining (p = 0.018), but was not observed between strong and moderate PD-1 staining (p = 0.146). Conclusions: PD-1 expression may be a useful indicator for a worse prognosis in UTUC patients who undergo radical nephroureterectomy. Targeting therapy against PD-1 might be a promising therapeutic modality for UTUC.

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