Faculty Opinions recommendation of Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish.

Mitochondrial pyruvate carrier (MPC), which is essential for mitochondrial pyruvate usage, mediates the transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness. However, the mechanism by which MPC expression is regulated is largely unknown. In this study, we showed that MPC1 is down-regulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1 alpha (PGC-1α). We also demonstrated that overexpression of PGC-1α stimulates MPC1 transcription, while depletion of PGC-1α by siRNA suppresses MPC expression. We found that PGC-1α interacts with estrogen-related receptor-alpha (ERR-α) and recruits it to the ERR-α response element motif located in the proximal MPC1 promoter, resulting in efficient activation of MPC1 expression. Furthermore, the MPC inhibitor, UK5099, blocked PGC-1α-induced pyruvate-dependent mitochondrial oxygen consumption. Taken together, our results suggest that MPC1 is a novel target gene of PGC-1α. In addition, low expression of PGC-1α in human RCC might contribute to the reduced expression of MPC, resulting in impaired mitochondrial respiratory capacity in RCC by limiting the transport of pyruvate into the mitochondrial matrix.

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Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00023.2017 ◽

2017 ◽

Vol 313 (6) ◽

pp. L1016-L1029 ◽

Cited By ~ 21

Author(s):

Siân Lax ◽

Julie Rayes ◽

Surasak Wichaiyo ◽

Elizabeth J. Haining ◽

Kate Lowe ◽

...

Keyword(s):

Alveolar Macrophages ◽

Therapeutic Intervention ◽

Arterial Oxygen Saturation ◽

Arterial Oxygen ◽

Type I ◽

Vascular Integrity ◽

Platelet Receptor ◽

Patients At Risk ◽

Novel Target ◽

Deficient Mice

There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS.

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Identification ofptproas a novel target gene of Wnt signaling and its potential role as a receptor for Wnt

FEBS Letters ◽

10.1016/j.febslet.2010.08.034 ◽

2010 ◽

Vol 584 (18) ◽

pp. 3923-3928 ◽

Cited By ~ 10

Author(s):

Minseong Kim ◽

Hanjun Kim ◽

Eek-hoon Jho

Keyword(s):

Wnt Signaling ◽

Target Gene ◽

Potential Role ◽

Novel Target

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CARD11 is a novel target of miR-181b that is upregulated in chronic lymphocytic leukemia

Biomarkers in Medicine ◽

10.2217/bmm-2020-0601 ◽

2021 ◽

Author(s):

Zhen Kou ◽

Min Mao ◽

Hong Liu ◽

Xiaomin Wang ◽

Zengsheng Wang ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Target Gene ◽

Target Genes ◽

Prognostic Indicator ◽

Lymphocytic Leukemia ◽

Poor Survival ◽

Kaplan Meier ◽

Poor Prognostic Indicator ◽

Novel Target

Aim: To investigate the targets of miR-181b in patients with chronic lymphocytic leukemia (CLL). Materials & methods: The bioinformatic softwares were used to indicate the key target genes associated with miR-181b, and the results were verified in CLL patient samples and 293T cells. Results: CARD11 is a potential target gene of miR-181b, an inverse relationship was revealed between the expression of CARD11 and miR-181b in 104 CLL patients, and it was confirmed in vitro with luciferase assays and western blotting. Kaplan–Meier analysis showed that CLL patients with high CARD11 expression demonstrated poor survival. Conclusion: CARD11 is a novel target of miR-181b that is upregulated, which could be a poor prognostic indicator for CLL patients.

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The Alpha-1-Fetoprotein (AFP) – A novel target gene for p63

10.1055/s-0040-1722066 ◽

2021 ◽

Author(s):

K Gülow ◽

E Ostheim ◽

M Müller-Schilling

Keyword(s):

Target Gene ◽

Novel Target

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WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability

Gastroenterology ◽

10.1053/gast.2001.29570 ◽

2001 ◽

Vol 121 (6) ◽

pp. 1275-1280 ◽

Cited By ~ 33

Author(s):

Lin Thorstensen ◽

Chieu B. Diep ◽

Gunn I. Meling ◽

Trude H. Aagesen ◽

Christian H. Ahrens ◽

...

Keyword(s):

Microsatellite Instability ◽

Signaling Pathway ◽

Target Gene ◽

Colorectal Carcinomas ◽

Novel Target

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Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy

Scientific Reports ◽

10.1038/srep36146 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 13

Author(s):

Chun-Mei Tang ◽

Fang-zhou Liu ◽

Jie-Ning Zhu ◽

Yong-Heng Fu ◽

Qiu-Xiong Lin ◽

...

Keyword(s):

Angiotensin Ii ◽

Target Gene ◽

Cardiomyocyte Hypertrophy ◽

Novel Target ◽

Enhancer Factor

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The CDK inhibitor p21 is a novel target gene of ATF4 and contributes to cell survival under ER stress

FEBS Letters ◽

10.1002/1873-3468.12869 ◽

2017 ◽

Vol 591 (21) ◽

pp. 3682-3691 ◽

Cited By ~ 14

Author(s):

Yasumichi Inoue ◽

Shiori Kawachi ◽

Tsubasa Ohkubo ◽

Mai Nagasaka ◽

Shogo Ito ◽

...

Keyword(s):

Er Stress ◽

Cell Survival ◽

Target Gene ◽

Cdk Inhibitor ◽

Novel Target

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PTP4A3, A Novel Target Gene of HIF-1alpha, Participates in Benzene-Induced Cell Proliferation Inhibition and Apoptosis through PI3K/AKT Pathway

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17030910 ◽

2020 ◽

Vol 17 (3) ◽

pp. 910

Author(s):

Yunqiu Pu ◽

Fengxia Sun ◽

Rongli Sun ◽

Zhaodi Man ◽

Shuangbin Ji ◽

...

Keyword(s):

Cell Proliferation ◽

Target Gene ◽

Akt Pathway ◽

Proliferation Inhibition ◽

Cell Proliferation Inhibition ◽

A Cell ◽

Novel Target ◽

In Cells

Benzene, a commonly used chemical, has been confirmed to specifically affect the hematopoietic system as well as overall human health. PTP4A3 is overexpressed in leukemia cells and is related to cell proliferation. We previously found that HIF-1alpha was involved in benzene toxicity and PTP4A3 may be the target gene of HIF-1alpha via ChIP-seq. The aim of this study is to confirm the relationship between HIF-1alpha and PTP4A3 in benzene toxicity, as well as the function of PTP4A3 on cell toxicity induced by 1,4-benzoquinone (1,4-BQ). Our results indicate that HIF-1alpha could regulate PTP4A3 with in vivo and in vitro experiments. A cell line with suppressed PTP4A3 was established to investigate the function of PTP4A3 in 1,4-BQ toxicity in vitro. The results revealed that cell proliferation inhibition was more aggravated in PTP4A3 low-expression cells than in the control cells after 1,4-BQ treatment. The relative oxygen species (ROS) significantly increased in cells with inhibited PTP4A3, while the rise was inferior to the control cells at the 20 μM 1,4-BQ group. An increase in DNA damage was seen in PTP4A3 down-regulated cells at the 10 μM 1,4-BQ group, whereas the results reversed at the concentration of 20 μM. Moreover, the apoptosis rate increased higher in down-regulated PTP4A3 cells after 1,4-BQ exposure. In addition, PI3K/AKT pathway was significantly restrained in cells with inhibited PTP4A3 after 1,4-BQ treatment. Our results indicate that HIF-1alpha may regulate PTP4A3 to be involved in benzene toxicity. Inhibition of PTP4A3 could aggravate cell proliferation suppression and apoptosis by regulating PI3K/AKT pathway after 1,4-BQ treatment.

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