MiR-140-3p Downregulation in Association with PDL-1 Overexpression in Many Cancers: A Review from the Literature Using Predictive Bioinformatics Tools

Kapodistrias, Nikolaos; Bobori, Catherine; Theocharopoulou, Georgia

doi:10.1007/978-3-319-56246-9_18

Cited by 19 publications

(16 citation statements)

References 29 publications

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“…In addition, previous experiments demonstrated that decreased expression of ZO-1, occludin, and claudin-5 increased BTB permeability 31 . Our study demonstrated that the expression of miR-140-3p was suppressed in GECs, and some literature reported that miR-140-3p was downregulated in many tissue cancers 12 , and its expression in lung cancer cells was lower than that in normal lung epithelial cells 32 , which was consistent with our results. In addition to regulating the expression of genes related to the nervous system, miR-140-3p can also regulate the other target genes expression 33 .…”

Section: Discussionsupporting

confidence: 92%

“…MicroRNAs (miRNAs) are noncoding, single-stranded, small RNA molecules with 18–25 nucleotides in length that can inhibit gene expression at the post-transcriptional level through nucleotide base pairings between complementary seed sequences of miRNAs and the target gene 3′untranslated regions (3′-UTR) 12 . Some miRNAs are considered to be proto-oncogenes and tumor suppressor genes, which are used as novel and promising therapeutic targets for cancer treatment by negatively regulating transcription or translation of target gene 1 , 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have found that miRNA is involved in the regulation of BTB permeability 13 , suggesting that miRNA is closely related to the function of endothelial cells. It has been reported that miR-140-3p is downregulated in many tissue cancers 12 . Similary, in our present application of miRNA microarray analysis technology, we found that the expression of miR-140-3p in the BTB group was significantly downregulated, suggesting that miR-140-3p may be related to the change of BTB permeability.…”

Section: Introductionmentioning

confidence: 99%

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Long non-coding RNA MIAT regulates blood tumor barrier permeability by functioning as a competing endogenous RNA

Xue

Wang

et al. 2020

Cell Death Dis

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Blood–tumor barrier (BTB) presents a major obstacle to brain drug delivery. Therefore, it is urgent to enhance BTB permeability for the treatment of glioma. In this study, we demonstrated that MIAT, ZAK, and phosphorylated NFκB-p65 (p-NFκB-p65) were upregulated, while miR-140-3p was downregulated in glioma-exposed endothelial cells (GECs) of BTB compared with those in endothelial cells cocultured with astrocytes (ECs) of blood–brain barrier (BBB). MIAT inhibited miR-140-3p expression, increased the expression of ZAK, enhanced the ratio of p-NFκB-p65:NFκB-p65, and promoted the endothelial leakage of BTB. Our current study revealed that miR-140-3p was complementary to the ZAK 3′untranslated regions (3′-UTR), and luciferase activity of ZAK was inhibited by miR-140-3p in 293T cells. MiR-140-3p silencing resulted in an increase in BTB permeability by targeting ZAK, while overexpression of miR-140-3p had the opposite results in GECs of BTB. Overexpression of ZAK induced an increase in BTB permeability, and this effect was related to ZAK’s ability to mediate phosphorylation of NFκB-p65. Conversely, ZAK silencing get opposite results in GECs of BTB. As a molecular sponge of miR-140-3p, MIAT attenuated its negative regulation of the target gene ZAK by adsorbing miR-140-3p. P-NFκB-p65 as a transcription factor negatively regulated the expression of TJ-associated proteins by means of chip assay and luciferase assay. Single or combined application of MIAT and miR-140-3p effectively promoted antitumor drug doxorubicin (Dox) across BTB to induce apoptosis of glioma cells. In summary, MIAT functioned as a miR-140-3p sponge to regulate the expression of its target gene ZAK, which contribution to phosphorylation of NFκB-p65 was associated with an increase in BTB permeability by down-regulating the expression of TJ associated proteins, thereby promoting Dox delivery across BTB. These results might provide a novel strategy and target for chemotherapy of glioma.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long non-coding RNA MIAT regulates blood tumor barrier permeability by functioning as a competing endogenous RNA

Xue

Wang

et al. 2020

Cell Death Dis

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“…evidence has indicated that mirnas regulate Pd-l1 expression in cancer (36). For example, downregulation of mir-140-3p is closely associated with overexpression of Pdl-1 in many cancers, including breast and lung cancer (37). in malignant pleural mesothelioma, tumor suppressor gene mirnas (mir-15b, mir-16, mir-193a-3p, mir-195, and mir-200c) downregulate the expression of Pd-l1 (38).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑140 suppresses Helicobacter pylori‑positive gastric cancer growth by enhancing the antitumor immune response

Zhao

Liu

et al. 2019

Mol Med Report

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immune checkpoint blockade is a promising therapeutic strategy against various human malignancies. Micrornas (mirnas/mirs) regulate gene expression, by repressing mrna translation or promoting its degradation. The aim of the current study was to investigate the role and molecular mechanisms of mir-140 in Helicobacter pylori (Hp)-associated gastric cancer, and to examine its relationship with immune function in gastric cancer. Gastritis tissue samples from gastritis patients, and gastric cancer tissue samples from gastric cancer patients were collected for mir-140 expression detection. mir-140 expression was detected using reverse transcription-quantitative polymerase chain reaction, and protein expression was measured by western blotting. TargetScan and dual luciferase reporter assays were used to reveal the association between mir-140 and programmed cell death-ligand 1 (Pd-l1). BGc823 cell proliferation was detected by MTT assays. Ex vivo immune analysis by flow cytometry and ELISA were used to analyze immune function. it was demonstrated that mir-140 expression was significantly reduced in Hp-positive gastric cancer. PD-L1 was confirmed as a direct target of miR-140 in gastric cancer cells. In addition, PD-L1 expression was significantly increased in Hp-positive gastric cancer. overexpression of miR-140 significantly suppressed gastric cancer cell proliferation through regulating Pd-l1 expression. In vivo experiments also revealed that mir-140 markedly repressed tumor growth in the c57Bl/6 mice. Furthermore, it was determined that the tumor-suppressive role of mir-140 in gastric cancer was associated with increased cytotoxic cd8 + T cell and reduced myeloid-derived suppressive and regulatory T cell infiltration. miR-140 significantly prevented mammalian target of rapamycin signaling in gastric cancer cells. notably, these mir-140 overexpression-induced alterations were inhibited by PD-L1 plasmid. These findings indicated that miR-140 exerted an anti-gastric cancer effect by targeting immune checkpoint molecule Pd-l1. Thus, mir-140 may be a promising and novel immunotherapeutic target for gastric cancer treatment.

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“…Previous studies have found that miR-140 levels are negatively correlated with PD-L1 expression, while PD-L1 expression is positively correlated with cyclin E expression [21, 22]. We therefore hypothesized a relationship between miR-140, PD-L1, and cyclin E. To investigate their roles in expression of cyclin E, the expression of miR-140 and PD-L1were manipulated.…”

Section: Resultsmentioning

confidence: 99%

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

Xie

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. Methods: We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and β-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. Results: We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3’ UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. Conclusion: We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.

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MiR-140-3p Downregulation in Association with PDL-1 Overexpression in Many Cancers: A Review from the Literature Using Predictive Bioinformatics Tools

Cited by 19 publications

References 29 publications

Long non-coding RNA MIAT regulates blood tumor barrier permeability by functioning as a competing endogenous RNA

Long non-coding RNA MIAT regulates blood tumor barrier permeability by functioning as a competing endogenous RNA

MicroRNA‑140 suppresses Helicobacter pylori‑positive gastric cancer growth by enhancing the antitumor immune response

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

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