GmBTB/POZ promotes the ubiquitination and degradation of LHP1 to regulate the response of soybean to Phytophthora sojae

AbstractPhytophthora sojae is a pathogen that causes stem and root rot in soybean (Glycine max [L.] Merr.). We previously demonstrated that GmBTB/POZ, a BTB/POZ domain-containing nuclear protein, enhances resistance to P. sojae in soybean, via a process that depends on salicylic acid (SA). Here, we demonstrate that GmBTB/POZ associates directly with soybean LIKE HETEROCHROMATIN PROTEIN1 (GmLHP1) in vitro and in vivo and promotes its ubiquitination and degradation. Both overexpression and RNA interference analysis of transgenic lines demonstrate that GmLHP1 negatively regulates the response of soybean to P. sojae by reducing SA levels and repressing GmPR1 expression. The WRKY transcription factor gene, GmWRKY40, a SA-induced gene in the SA signaling pathway, is targeted by GmLHP1, which represses its expression via at least two mechanisms (directly binding to its promoter and impairing SA accumulation). Furthermore, the nuclear localization of GmLHP1 is required for the GmLHP1-mediated negative regulation of immunity, SA levels and the suppression of GmWRKY40 expression. Finally, GmBTB/POZ releases GmLHP1-regulated GmWRKY40 suppression and increases resistance to P. sojae in GmLHP1-OE hairy roots. These findings uncover a regulatory mechanism by which GmBTB/POZ-GmLHP1 modulates resistance to P. sojae in soybean, likely by regulating the expression of downstream target gene GmWRKY40.

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MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

Cancer Cell International ◽

10.1186/s12935-019-1017-5 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 8

Author(s):

Yangyang Li ◽

Jia Xu ◽

Jiale Zhang ◽

Jie Zhang ◽

Jian Zhang ◽

...

Keyword(s):

Target Gene ◽

Glioma Cells ◽

Downstream Target ◽

Downstream Target Gene ◽

Direct Target ◽

Proliferation Assays ◽

The Relationship ◽

Proliferation In Vitro

Abstract Background Glioma is considered one of the most common tumors and has a poor prognosis. Recently, microRNAs (miRNAs) have been reported to be strongly linked to various human tumors including glioma. In this study, we investigated a new anticancer miRNA, miR-346, to determine the effects and mechanism of miR-346 and its downstream target gene NFIB on tumors. Methods Lentivirus transfection, real-time PCR, western blotting, immunohistochemistry, cell proliferation assays, and mouse experiments were used to examine the relationship between miR-346 and its regulation of NFIB in glioma cells. Results The expression of miR-346 was downregulated in glioma cells. Overexpression of miR-346 arrested the cell cycle of glioma cells and inhibited their proliferation in vitro and in vivo. NFIB was a direct target of miR-346, whose expression was reduced by the miRNA. Overexpression of NFIB reversed all tested functions of miR-346. Conclusion miR-346 inhibited the growth of glioma cells by targeting NFIB and may be a new prognostic and diagnostic biomarker for glioma.

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Potential mechanisms of microRNA-141-3p to alleviate chronic inflammatory pain by downregulation of downstream target gene HMGB1: in vitro and in vivo studies

Gene Therapy ◽

10.1038/gt.2017.28 ◽

2017 ◽

Vol 24 (6) ◽

pp. 353-360 ◽

Cited By ~ 20

Author(s):

W-S Shen ◽

X-Q Xu ◽

N-N Zhai ◽

Z-S Zhou ◽

J Shao ◽

...

Keyword(s):

Inflammatory Pain ◽

Target Gene ◽

In Vivo Studies ◽

Chronic Inflammatory Pain ◽

Downstream Target ◽

Downstream Target Gene

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Aryl Hydrocarbon Receptor: Its Regulation and Roles in Transformation and Tumorigenesis

Current Drug Targets ◽

10.2174/1389450120666181109092225 ◽

2019 ◽

Vol 20 (6) ◽

pp. 625-634 ◽

Cited By ~ 1

Author(s):

Xun Che ◽

Wei Dai

Keyword(s):

Target Gene ◽

Tumor Development ◽

Environmental Response ◽

Carcinogenic Effect ◽

Post Translational Modifications ◽

Downstream Target ◽

Aryl Hydrocarbon ◽

Downstream Target Gene ◽

Major Mediator

AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.

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MiR-30a-5p inhibits proliferation, migration and invasion of nasopharyngeal carcinoma cells by targeting NUCB2

Human & Experimental Toxicology ◽

10.1177/0960327121991913 ◽

2021 ◽

pp. 096032712199191

Author(s):

M Li ◽

Y Wang ◽

Q Zhao ◽

W Ma ◽

J Liu

Keyword(s):

Nasopharyngeal Carcinoma ◽

Tumor Growth ◽

Carcinoma Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Binding Interaction ◽

Downstream Target ◽

Downstream Target Gene

Background: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor arising in the nasopharynx. MicroRNAs (miRNAs) are elucidated to exert tumor-suppressing function in human cancers. Numerous studies have manifested that miR-30a-5p serves as an anti-oncogene in various cancers. Objective: To research the biological function and molecular mechanism of miR-30a-5p in NPC. Methods: The morphology of NPC tissues was revealed by H&E staining. Transwell and wound healing assays were applied to investigate the effects of miR-30a-5p on NPC cell migration. The binding interaction between miR-30a-5p and nucleobindin 2 (NUCB2) was identified by luciferase reporter assay. Xenograft nude mice were used to detect the influence of miR-30a-5p on NPC tumor growth. Results: MiR-30a-5p was downregulated in NPC tissues and cells. The overexpression ofmiR-30a-5p inhibited proliferation, migration and invasion abilities of NPC cells. Moreover, NUCB2 was revealed to be a downstream target gene of miR-30a-5p, and knockdown of NUCB2 repressed the malignant behaviors of NPC cells and tumor growth. Additionally, rescue experiments revealed that miR-30a-5p suppressed the proliferation, migration and invasion of NPC cells via targeting NUCB2 in vitro. Meanwhile, in vivo assays depicted that NUCB2 overexpression rescued the effects induced by miR-30a-5p upregulation on tumor growth. Conclusion: MiR-30a-5p modulates NPC progression by targeting NUCB2. These findings lay a foundation for exploring the clinical treatment of NPC.

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Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney

Development ◽

10.1242/dev.129.22.5301 ◽

2002 ◽

Vol 129 (22) ◽

pp. 5301-5312 ◽

Cited By ~ 5

Author(s):

Jing Yu ◽

Thomas J. Carroll ◽

Andrew P. McMahon

Keyword(s):

Smooth Muscle ◽

Sonic Hedgehog ◽

Target Gene ◽

Kidney Development ◽

Metanephric Mesenchyme ◽

Downstream Target ◽

Proliferation And Differentiation ◽

Collecting Ducts ◽

Downstream Target Gene

Signaling by the ureteric bud epithelium is essential for survival,proliferation and differentiation of the metanephric mesenchyme during kidney development. Most studies that have addressed ureteric signaling have focused on the proximal, branching, ureteric epithelium. We demonstrate that sonic hedgehog is expressed in the ureteric epithelium of the distal, non-branching medullary collecting ducts and continues into the epithelium of the ureter— the urinary outflow tract that connects the kidney with the bladder. Upregulation of patched 1, the sonic hedgehog receptor and a downstream target gene of the signaling pathway in the mesenchyme surrounding the distal collecting ducts and the ureter suggests that sonic hedgehog acts as a paracrine signal. In vivo and in vitro analyses demonstrate that sonic hedgehog promotes mesenchymal cell proliferation, regulates the timing of differentiation of smooth muscle progenitor cells, and sets the pattern of mesenchymal differentiation through its dose-dependent inhibition of smooth muscle formation. In addition, we also show that bone morphogenetic protein 4 is a downstream target gene of sonic hedgehog signaling in kidney stroma and ureteral mesenchyme, but does not mediate the effects of sonic hedgehog in the control of mesenchymal proliferation.

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KIAA1429 and ALKBH5 Oppositely Influence Aortic Dissection Progression via Regulating the Maturation of Pri-miR-143-3p in an m6A-Dependent Manner

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.668377 ◽

2021 ◽

Vol 9 ◽

Author(s):

Peng Wang ◽

Zhiwei Wang ◽

Min Zhang ◽

Qi Wu ◽

Feng Shi ◽

...

Keyword(s):

Aortic Dissection ◽

Dependent Manner ◽

Loss Of Function ◽

Therapeutic Approaches ◽

Downstream Target ◽

Downstream Target Gene ◽

Molecular Mechanism Of Action ◽

New Research

Despite decades of study into aortic dissection (AD), a lethal cardiovascular emergency due to a tear in the aorta intima or bleeding within the aortic wall, leading to the separation of the different layers of it, the factors that influence its progression and the deeper regulatory mechanisms remain poorly understood. Nowadays, with the maturity of N6-methyladenosine (m6A) sequence technology, m6A modification, one type of RNA epigenesis, has gradually become a new research hotspot for epigenetic molecular regulation. Especially recently, increasing evidence has revealed that m6A modification functions as a pivotal post-transcriptional modification to influence the progression of multiple diseases. Based on these findings, it is reasonable to speculate that m6A modification may affect the onset and progression of AD. To explore the validity of our conjecture and to elucidate its underlying molecular mechanism of action, we conducted the present study. In this study, we found that KIAA1429 is downregulated while ALKBH5 is upregulated in aortic tissues from AD patients. Furthermore, gain- and loss-of-function studies showed that KIAA1429 and ALKBH5 can oppositely regulate HASMC proliferation, HAEC apoptosis, and AD progression in AngII-infused mice. Mechanistically, we demonstrated that KIAA1429/ALKBH5-mediated m6A modifications can regulate the processing of pri-miR-143-3p through interacting with the microprocessor protein DGCR8, thus indirectly regulating the downstream target gene of mature miR-143-3p, DDX6, to perform their biological functions in vitro and in vivo. Our findings have revealed a novel connection between m6A modification and AD progression and may provide a novel molecular basis for subsequent researchers to search for novel therapeutic approaches to improve the health of patients struggling with AD.

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Long noncoding RNA PVT1 promoted gallbladder cancer proliferation by epigenetically suppressing miR-18b-5p via DNA methylation

Cell Death and Disease ◽

10.1038/s41419-020-03080-x ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Longyang Jin ◽

Qiang Cai ◽

Shouhua Wang ◽

Shuqing Wang ◽

Jiandong Wang ◽

...

Keyword(s):

Dna Methylation ◽

Gallbladder Cancer ◽

Noncoding Rna ◽

Biliary Tree ◽

Cancer Proliferation ◽

Downstream Target ◽

Downstream Target Gene ◽

Proliferation In Vitro

Abstract Gallbladder cancer (GBC) accounts for 85–90% malignancies of the biliary tree worldwide. Considerable evidence has demonstrated that dysregulation of lncRNAs is involved in the progression of cancer. LncRNA PVT1 has been reported to play important roles in various cancers, but its role in gallbladder cancer remains unknown. In the present study, we found that PVT1 was upregulated in GBC tissues and cells, and its upregulation was related with poor prognosis in GBC patients. PVT1 promoted GBC cells proliferation in vitro and in vivo. Mechanistically, PVT1 recruited DNMT1 via EZH2 to the miR-18b-5p DNA promoter and suppressed the transcription of miR-18b-5p through DNA methylation. Moreover, HIF1A was proved to be the downstream target gene of miR-18b-5p and PVT1 regulated GBC cells proliferation via HIF1A. In conclusion, our studies clarified the PVT1/miR-18b-5p/HIF1A regulation axis and indicated that PVT1 could be a potential therapeutic target for GBC.

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Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3

Cell Death and Disease ◽

10.1038/s41419-021-03775-9 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Shuaishuai Zhuo ◽

Miaomiao Sun ◽

Rumeng Bai ◽

Die Lu ◽

Shihao Di ◽

...

Keyword(s):

Gastric Cancer ◽

Western Blot ◽

Molecular Mechanisms ◽

Downstream Target ◽

Non Coding Rna ◽

Downstream Target Gene ◽

Proliferation And Metastasis ◽

And Migration

AbstractGastric cancer (GC) is one of the most common malignancies worldwide, but its molecular mechanisms remain unclear. Increasing evidence indicates that long non-coding RNAs (LncRNAs) play a pivotal role in various cancers recently. Our present study focused on exploring the function of long intergenic non-coding RNA 00473 (LINC00473) in GC. In this study, we found that LINC00473 expression was aberrantly increased in tumor tissues compared with the paired para-cancerous tissues. The expression of high LINC00473 in GC was notably correlated with a higher risk of lymphatic metastasis, a higher incidence of vascular cancer embolus, and advanced TNM stage. Further experiments showed that the overexpression of LINC00473 could promote the proliferation and metastasis of GC cells both in vitro and in vivo. The apoptosis of GC cells increased significantly by the decrease of LINC00473. Mechanistically, LINC00473 could sponge miR-16-5p in the cytoplasm and relieve its suppression of CCND2. Moreover, AQP3 was found to be a significant downstream target gene for LINC00473 through RNA transcriptome sequencing, as demonstrated by qRT-PCR and western blot. Overexpression of LINC00473 can partially reverse the effects of AQP3 decrease on GC proliferation and metastasis. LINC00473 regulated AQP3 expression through CREB was confirmed by western blot. Our research indicates that LINC00473/miR-16-5p/CCND2 axis plays a role in the proliferation of GC and modulates AQP3 to influence GC cell metastasis, making it a potential therapeutic target for GC.

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A Phytophthora effector recruits a host cytoplasmic transacetylase into nuclear speckles to enhance plant susceptibility

eLife ◽

10.7554/elife.40039 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 13

Author(s):

Haiyang Li ◽

Haonan Wang ◽

Maofeng Jing ◽

Jinyi Zhu ◽

Baodian Guo ◽

...

Keyword(s):

Root Rot ◽

Plant Immunity ◽

Phytophthora Sojae ◽

Host Immunity ◽

Effector Proteins ◽

Nuclear Speckles ◽

Rxlr Effector ◽

Plant Susceptibility

Oomycete pathogens secrete host cell-entering effector proteins to manipulate host immunity during infection. We previously showed that PsAvh52, an early-induced RxLR effector secreted from the soybean root rot pathogen, Phytophthora sojae, could suppress plant immunity. Here, we found that PsAvh52 is required for full virulence on soybean and binds to a novel soybean transacetylase, GmTAP1, in vivo and in vitro. PsAvh52 could cause GmTAP1 to relocate into the nucleus where GmTAP1 could acetylate histones H2A and H3 during early infection, thereby promoting susceptibility to P. sojae. In the absence of PsAvh52, GmTAP1 remained confined to the cytoplasm and did not modify plant susceptibility. These results demonstrate that GmTAP1 is a susceptibility factor that is hijacked by PsAvh52 in order to promote epigenetic modifications that enhance the susceptibility of soybean to P. sojae infection.

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