MicroRNA-138-5p Suppresses Non-small Cell Lung Cancer Cells by Targeting PD-L1/PD-1 to Regulate Tumor Microenvironment

Song, Nannan; P, Li; Song, Pingping; Li, Yintao; Zhou, Shuping; Su, Qinghong; Li, Xiaofan; Yu, Yong; Li, Pengfei; Feng, Ming; Zhang, Min; Lin, Wei

doi:10.3389/fcell.2020.00540

Cited by 39 publications

(43 citation statements)

References 61 publications

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“…We found by microarray analysis that miR-138-5p was upregulated in usual PSCC. miR-138-5p is a tumor suppressor that targets PD-L1 [ 70 , 71 , 72 ]. Therefore, it would be interesting to investigate the potential role of miR-138-5p as a biomarker for therapy selection using checkpoint inhibitors in PSCC patients in the future.…”

Section: Discussionmentioning

confidence: 99%

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

Ayoubian

Heinzelmann

Hölters

et al. 2021

Cancers

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Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

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Section: Discussionmentioning

confidence: 99%

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

Ayoubian

Heinzelmann

Hölters

et al. 2021

Cancers

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“…According to previous reports, miR-138-5p could target PDL1 to inhibit tumorigenesis in colorectal cancer and lung cancer (Zhao, Yu et al, 2016;Song, Li et al, 2020). Ashizawa et al also revealed a regulatory mechanism of PDL1 expression that miR-148a-3p decreased PDL1 expression and suppressed immune evasion in colorectal cancer cells (Ashizawa, Okayama et al, 2019).…”

Section: Discussionmentioning

confidence: 93%

circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis

Jiang

Hou

Liu

et al. 2021

J Pharmacol Exp Ther

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Background: Recently, circular RNA (circRNA) was reported to be a significant participant in the development of tumorigenesis, including colorectal cancer. Therefore, we aimed to clarify the precise role of circ-keratin 6C (circ-KRT6C) in colorectal cancer progression. Methods: The relative expression levels of circ-KRT6C, microRNA-16-5p (miR-485-3p), and programmed cell death receptor ligand 1 (PDL1) were analyzed by real-time quantitative polymerase chain reaction and western blot assays. The proliferation was assessed by cell count kit 8 and colony-forming assays. The apoptotic cells were determined by flow cytometry assay. The migration and invasion were analyzed by transwell assay. Colorectal cancer cells were co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells to assess immune response. The interaction relationships among circ-KRT6C, miR-485-3p, and PDL1 were examined by dual-luciferase reporter assay. The effects of circ-KRT6C inhibition in vivo was analyzed by an animal experiment. Results: Circ-KRT6C was overexpressed in colorectal cancer tissues and cells, and its level was associated with overall survival time of colorectal cancer patients. The suppression of circ-KRT6C suppressed growth, migration, invasion, and immune escape while stimulated apoptosis in colorectal cancer cells, which was abolished by shortage of miR-485-3p. In addition, overexpression of miR-485-3p repressed malignant progression and immune evasion of colorectal cancer by targeting PDL1, implying that PDL1 was a functional target of miR-485-3p. A xenograft experiment also suggested that circ-KRT6C inhibition could repress tumor growth in vivo. Conclusion: Circ-KRT6C could increase PDL1 expression by functioning as a miR-485-3p sponge, which promoted malignant progression and immune evasion of colorectal cancer cells.

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“…As miR-25-5p may be sponged via phenanthriplatin-mediated upregulation of lnc-MRPL39-10 (Table 2), this miRNA could be downregulated in A549 cells, which is associated with anti-cancer effect via PI3K signaling [25]. Reduction of AGO2-1, COX7A1-2, and SLC26A3-1 by phenanthriplatin would also be expected to lead to increased miR-138-5p and − 608, whose expression modulates PTEN/PI3K/AKT signaling and is associated in A549 cells with anticancer effect [23,31,[45][46][47]. In retinoblastoma tumors, increased miR-4516 expression promotes tumor growth through the PTEN/AKT pathway [32].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, miR-138-5p and miR-608 are potentially not subject to sponging in A549 cells treated with the monofunctional complex as their lncRNA targets are downregulated, but in IMR90 cells, these miRNA could be sponged by upregulated lnc-TMEM243-1 (Table 2, 3, 4). Therefore, reduced expression of miR-138-5p and − 608 due to TMEM243-1 decoying in IMR90 cells could lead to reduced cytotoxicity via TGF-β signaling (miR-138-5p) or Wnt/β-catenin and TGF-β signaling (miR-608) as suggested by the effects of suppressing these miRNAs in A549 cells [23,[46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling

Monroe

Moolani

Irihamye

et al. 2021

Preprint

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The monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lung cancer and IMR90 lung fibroblast cells for 24 hours with either cisplatin, phenanthriplatin or a solvent control, and then performed microarray analysis to identify regulated lncRNAs. RNA22 v2 microRNA software was subsequently used to identify microRNAs (miRNAs) that might be suppressed by the most regulated lncRNAs. We found that miR-25-5p, -30a-3p, -138-5p, -149-3p, -185-5p, -378j, -608, -650, -708-5p, -1253, -1254, -4458, and − 4516, were predicted to target the cisplatin upregulated lncRNAs, IMMP2L-1, CBR3-1 and ATAD2B-5, and the phenanthriplatin downregulated lncRNAs, AGO2-1, COX7A1-2 and SLC26A3-1. The signaling pathways associated with these miRNAs suggests that phenanthriplatin may modulate Wnt/β-catenin and TGF-β signaling through the MAPK/ERK and PTEN/AKT pathways differently than cisplatin. Further, as some of these miRNAs may be subject to dissimilar lncRNA targeting in A549 and IMR90 cells, the monofunctional complex may not cause toxicity in normal lung compared to cancer cells by acting through distinct lncRNA and miRNA networks.

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MicroRNA-138-5p Suppresses Non-small Cell Lung Cancer Cells by Targeting PD-L1/PD-1 to Regulate Tumor Microenvironment

Cited by 39 publications

References 61 publications

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis

Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling

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