Programmed cell death 4 protein (Pdcd4) and homeodomain-interacting protein kinase 2 (Hipk2) antagonistically control translation of Hipk2 mRNA

Ohnheiser, Johanna; Ferlemann, Eva; Haas, Astrid; Müller, Jan Paul; Werwein, Eugen; Fehler, Olesja; Biyanee, Abhiruchi; Klempnauer, Karl‐Heinz

doi:10.1016/j.bbamcr.2015.03.008

Cited by 10 publications

(8 citation statements)

References 57 publications

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“…PDCD4 is a highly conserved RNA-binding protein that inhibits the translation of specific mRNAs [9]. As a significant tumor suppressor, PDCD4 affects translation and transcription of multiple genes, and regulates various signal transduction pathways [10].…”

Section: Introductionmentioning

confidence: 99%

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Zhang¹,

He²,

Shi³

2017

Cell Physiol Biochem

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Background/Aims: This study aimed to analyze the impact of microRNA-499 (miR-499) on the inflammatory damage of endothelial cells during coronary artery disease (CAD) via the targeting of PDCD4 through the NF-kB/ TNF-α signaling pathway. Methods: A total of 216 CAD patients (CAD group) and 90 healthy people (normal group) were enrolled in our study. Endothelial cells were collected and assigned into normal, OX-LDL, negative control (NC), miR-499 inhibitor, miR-499 mimic, PDCD4 siRNA, and miR-499 inhibitor + PDCD4 siRNA groups. The qRT-PCR and western blotting were performed to detect the mRNA and protein expression levels of PDCD4 and miR-499. The MTT assay was performed to determine cell viability, ELISA was performed to determine the expression levels of inflammatory factors, and flow cytometry assay to evaluate cell apoptosis. Results: Increased miR-499 expression and decreased PDCD4 expression in the plasma were observed in the CAD group compared with the normal group, demonstrating a negative correlation between miR-499 and PDCD4. Compared to the normal and miR-499 inhibitor groups, the survival rate of cells and PDCD4 expression were decreased; and the expressions of miR-499, IL-6, IL-8, IL-1β, TNF-α, NF-kB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all elevated in the OX-LDL, NC, miR-499 mimic, PDCD4 siRNA and miR-499 inhibitor + PDCD4 siRNA groups. Compared to the OX-LDL, NC and miR-499 inhibitor + PDCD4 siRNA groups, PDCD4 expression and the survival rate of cells were increased; and the IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 expression levels and the apoptosis rate were all reduced in the miR-499 inhibitor group. In the PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were lower, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all higher compared with the miR-499 mimic group. In the miR-499 inhibitor + PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were higher, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1, and MCP-1 and the apoptosis rate were all lower than those in the PDCD4 siRNA group. Conclusion: Down-regulated miR-499 expression increased PDCD4 expression and protected endothelial cells from inflammatory damage during CAD by inhibiting the NF-κB/TNF-α signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Zhang¹,

He²,

Shi³

2017

Cell Physiol Biochem

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“…HIPK1 was identified as a oncoprotein in lung adenocarcinoma cells ( 25 ). Additionally, HIPK1 mRNA was reported to be a translational target of PDCD4 ( 26 ). HIPK1 stimulates the translation of its own mRNA; PDCD4 may suppress the translation of HIPK1 mRNA by interfering with this auto-regulatory feedback mechanism ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Sipi soup inhibits cancer‑associated fibroblast activation and the inflammatory process by downregulating long non‑coding RNA HIPK1‑AS

Zhou

et al. 2018

Mol Med Report

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Sipi soup (SPS), the aqueous extract derived from the root bark of Sophora japonical L, Salix babylonica L., Morus alba L., as well as Amygdalus davidiana (Carr.) C. de Vos, is a traditional Chinese medicine frequently used to prevent and treat infection and inflammation. However, the role of SPS in cancer-associated fibroblasts (CAFs) require further investigation. In the present study, the effects of SPS on fibroblast inactivation and the underlying mechanism were investigated. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA expression levels of fibroblast activation protein (FAP), interleukin (IL)-6, α-smooth muscle actin (α-SMA) and programmed cell death 4 (PDCD4). Flow cytometry was used to evaluate cell apoptosis. Immunofluorescence was used to determine the number of activated fibroblasts. The present study reported that SPS treatment did not affect the proliferative apoptotic potential of fibroblasts. Treatment with HeLa cell culture medium (CM) induced a significant increase in the expression levels of FAP, IL-6 and α-SMA, but reduced the expression of PDCD4. SPS reversed the effects of HeLa CM on the expression of these genes. Analysis with a long non-coding (lnc)RNA array of numerous differentially expressed lncRNAs revealed that the expression levels of the lncRNA homeodomain-interacting protein kinase 1 antisense RNA (HIPK1-AS) were increased in cervicitis tissues and cervical squamous cell carcinoma tissues compared with in normal cervical tissues. HIPK1-AS expression levels were upregulated in response to HeLa CM, but were decreased under SPS treatment. The downregulation of HIPK1-AS expression via short hairpin RNA abolished the effects of HeLa CM on the expression of inflammation-associated genes. The findings of the present study suggested that SPS may prevent the progression of cervical cancer by inhibiting the activation of CAF and the inflammatory process by reducing HIPK1-AS expression.

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“…, 2013 ), and it is unclear whether this circular RNA is translated into a protein. The molecular mechanism allowing decreased HIPK2 synthesis is not known and might involve further regulatory proteins, such as PDCD4, which was recently identified as an antagonist of HIPK2 translation ( Ohnheiser et al. , 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…This is achieved by several layers of regulation taking place at several levels, including the control of HIPK2 translation and protein stability. The RNA-binding protein programmed cell death protein 4 (PDCD4) suppresses the translation of Hipk2 mRNA and thus limits its de novo protein synthesis ( Ohnheiser et al. , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

HIPK family kinases bind and regulate the function of the CCR4-NOT complex

Rodríguez-Gil

Ritter

Hornung

et al. 2016

MBoC

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Programmed cell death 4 protein (Pdcd4) and homeodomain-interacting protein kinase 2 (Hipk2) antagonistically control translation of Hipk2 mRNA

Cited by 10 publications

References 57 publications

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Sipi soup inhibits cancer‑associated fibroblast activation and the inflammatory process by downregulating long non‑coding RNA HIPK1‑AS

HIPK family kinases bind and regulate the function of the CCR4-NOT complex

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