The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

Liu, Jiahui; Li, Libo; Chao, Shuo; Liu, Yunhui; Liu, Xiaobai; Zheng, Jian; Chen, Jiajia; Gong, Wei; Teng, Hao Wei; Li, Zhen; Wang, Ping; Xue, Yixue

doi:10.3389/fncel.2017.00358

Cited by 18 publications

(13 citation statements)

References 47 publications

(60 reference statements)

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“…Therefore, the aberrant expression of CREBBP may have impact on calcification which is consistent with the results of the present study. Furthermore, it was reported that the translocation of CiTED1 is enhanced by the protein kinase C activator (27,28). a number of studies have set out to determine the role of mir-330-3p in different types of tumors, most of which have reported mir-330-3p-3p as a tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

“…For example, miR-330-3p plays a critical role in glioma, as well as in breast ( 29 ), liver, esophageal ( 30 ), lung, gastric, colon and prostate cancers ( 31 – 35 ). Although its role in cardiovascular calcification remains unclear, Liu et al ( 28 ) has proposed that miR-330-3p directs the proliferation of several types of cells, and demonstrated its negative influence of protein kinase C on the endothelial monocyte-activating polypeptide-II in the immortalized human brain endothelial cell line, hCMEC/D3. These findings indicate that miR-330-3p may be involved in the process of calcification in cardiovascular system, which was consistent with the results of the present study.…”

Section: Discussionmentioning

confidence: 99%

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Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP

Zheng

Líu

et al. 2020

Mol Med Rep

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one key risk factor of aortic valve stenosis in clinical practice is bicuspid aortic valve (BaV). increasing evidence indicates that numerous micrornas (mirs/mirnas) are involved in BaV calcification via their target genes. mir-330-3p was found to be involved in the deterioration of BAV calcification by miR profiling in human calcified BAV and tricuspid aortic valve (TAV) tissues in the present study and the underlying mechanism was investigated. rna sequencing was performed on four BaV and four TaV tissues from patients with aortic stenosis before these leaflets were examined for the expression levels of mir-330-3p and creB-binding protein (creBBP) by reverse transcription-Pcr. The alteration of functional factors associated with calcification was also assessed by Western blotting and immunohistochemistry in human aortic tissue samples. The putative target of mir-330-3p was detected by dual-luciferase assay in 293 cells. Furthermore, the influence of miR-330-3p expression on osteogenic progression was explored in cultured porcine valve interstitial cells (VICs). Rescue experiments of CRBBP were performed to confirm the influence of the miR-330-3p-CREBBP pathway in the calcification progress in porcine Vics. rna sequencing indicated distinct expression of miR-330-3p in human BAV tissues compared with TAV, which was then confirmed by PCR. CREBBP expression levels in human BAV and TAV leaflets also demonstrated the opposite alterations. This negative correlation was then confirmed in cultured porcine VICs. Under an osteogenic environment, cellular calcification was promoted in miR-330-3p-overexpressed porcine VICs expressing higher bone morphogenetic protein 2, Runt-related transcription factor 2, matrix metalloproteinase (MMP)-2, MMP-9 and collagen i compared with controls. rescue experiments further confirmed that miR-330-3p played its role via targeting creBBP in porcine Vics. collectively, miR-330-3p was upregulated in calcified BAV compared with TAV. The upregulation of miR-330-3p promotes the calcification progress partially via targeting creBBP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP

Zheng

Líu

et al. 2020

Mol Med Rep

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“…The blood–tumor barrier (BTB) locating between brain tumor cells and microvessels can severely block the entry of macromolecules from the blood into tumors, resulting in poor prognosis and low efficacy of glioma 2 , 3 . Although the growth of glioma can cause BTB partly damage, making it slightly more permeable than the blood–brain barrier (BBB), BTB is still a major obstacle to the delivery of anticancer drugs into the tumor 4 . Therefore, selective opening of BTB is the basis and prerequisite for the treatment of glioma 2 .…”

Section: Introductionmentioning

confidence: 99%

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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“…MicroRNAs (miRNAs) are a group of non-coding RNAs of about 22 nucleotides, which usually bind to the 3′ untranslated region (UTR) of mRNA, and negatively regulate expression of target genes at the post-transcriptional level. MiRNAs play important roles in biological function and are also involved in the regulation of BTB permeability 19,20 . Previous literature showed that miR-577 was downregulated in various types of tumors, including glioblastoma, hepatocellular carcinoma, colorectal cancer, et al 21–24 .…”

Section: Introductionmentioning

confidence: 99%

KHDRBS3 regulates the permeability of blood–tumor barrier via cDENND4C/miR-577 axis

Gao

Shen

et al. 2019

Cell Death Dis

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The existence of blood–tumor barrier (BTB) severely restricts the efficient delivery of antitumor drugs to cranial glioma tissues. Various strategies have been explored to increase BTB permeability. RNA-binding proteins and circular RNAs have recently emerged as potential regulators of endothelial cells functions. In this study, RNA-binding protein KH RNA-binding domain containing, signal transduction associated 3 (KHDRBS3) and circular RNA DENND4C (cDENND4C) were enriched in GECs. KHDRBS3 bound to cDENND4C and increased its stability. The knockdown of cDENND4C increased the permeability of BTB via downregulating the expressions of tight junction-related proteins. The miR-577 was lower expressed in GECs. The overexpressed miR-577 increased the permeability of BTB by reducing the tight junction-related protein expressions, and vice versa. Furthermore, cDENND4C acted as a molecular sponge of miR-577, which bound to miR-577 and inhibited its negative regulation of target genes ZO-1, occludin and claudin-1 to regulate BTB permeability. Single or combined treatment of KHDRBS3, cDENND4C, and miR-577 effectively promoted antitumor drug doxorubicin (DOX) across BTB to induce apoptosis of glioma cells. Collectively, the present study indicated that KHDRBS3 could regulate BTB permeability through the cDENND4C/miR-577 axis, which enhanced doxorubicin delivery across BTB. These findings may provide a novel strategy for chemotherapy of brain tumors.

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The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

Cited by 18 publications

References 47 publications

Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP

Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP

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

KHDRBS3 regulates the permeability of blood–tumor barrier via cDENND4C/miR-577 axis

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