Clusterin gene transcription is activated by caudal-related homeobox genes in intestinal epithelium

Caudal-related homeobox (Cdx) proteins play an important role in development and differentiation of the intestinal epithelium. Using cDNA differential display, we identified clusterin as a prominently induced gene in a Cdx2-regulated cellular model of intestinal differentiation. Transfection experiments and DNA-protein interaction assays showed that clusterin is an immediate downstream target gene for Cdx proteins. The distribution of clusterin protein in the intestine was assessed during development and in the adult epithelium using immunohistochemistry. In the adult mouse epithelium, clusterin protein was localized in both crypt and villus compartments but not in interstitial cells of the intestinal mucosa. Together, these data suggest that clusterin is a direct target gene for Cdx homeobox proteins, and the pattern of clusterin protein expression suggests that it is associated with the differentiated state in the intestinal epithelium.

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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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The Regulation of Downstream Target Gene AP-2γ by Transcription Factor OCT-4

ACTA AGRONOMICA SINICA ◽

10.3724/sp.j.1206.2012.00203 ◽

2013 ◽

Vol 40 (1) ◽

pp. 43

Author(s):

Xiao-Meng ZHAO ◽

Cheng WANG ◽

Xiao-Feng LI ◽

Xiao-Ting ZHANG ◽

Xi-Zhi LIU ◽

...

Keyword(s):

Transcription Factor ◽

Target Gene ◽

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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Identification ofTDRD1as a direct target gene ofERGin primary prostate cancer

International Journal of Cancer ◽

10.1002/ijc.28025 ◽

2013 ◽

Vol 133 (2) ◽

pp. 335-345 ◽

Cited By ~ 40

Author(s):

Joost L. Boormans ◽

Hanneke Korsten ◽

Angelique J.C. Ziel-van der Made ◽

Geert J.L.H. van Leenders ◽

Carola V. de Vos ◽

...

Keyword(s):

Prostate Cancer ◽

Target Gene ◽

Primary Prostate Cancer ◽

Direct Target Gene ◽

Direct Target

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ZNF16 (HZF1) promotes erythropoiesis and megakaryocytopoiesis via regulation of the c-KIT gene

Biochemical Journal ◽

10.1042/bj20130628 ◽

2014 ◽

Vol 458 (1) ◽

pp. 171-183 ◽

Cited By ~ 3

Author(s):

Jing Chen ◽

Xiao-Bo Li ◽

Rui Su ◽

Li Song ◽

Fang Wang ◽

...

Keyword(s):

Progenitor Cells ◽

Target Gene ◽

Megakaryocytic Differentiation ◽

Kit Gene ◽

Direct Target Gene ◽

Direct Target

The present study demonstrated that ZNF16 (HZF1) plays an important role in erythroid and megakaryocytic differentiation of human haematopoietic stem/progenitor cells, identified and validated c-KIT as a direct target gene of ZNF16, and demonstrated that ZNF16 functions via its regulation on the c-Kit/c-Raf/MEK/ERK/c-Jun/HEY1/GATA1 cascade.

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Abstract 355: Exercise Prevents Doxorubicin-induced Cardiotoxicity via Targeting Microrna-669a-5p in Mice

Circulation Research ◽

10.1161/res.117.suppl_1.355 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Yihua Bei ◽

Jiahong Xu ◽

Tianzhao Xu ◽

Ping Chen ◽

Lin Che ◽

...

Keyword(s):

Protective Effect ◽

Target Gene ◽

Contractile Function ◽

Cardiac Contractile Function ◽

Downstream Target ◽

Cardiac Contractile ◽

Downstream Target Gene ◽

Cardiac Ejection Fraction ◽

Response To Exercise ◽

Fractional Shortening

Doxorubicin (Dox)-induced cardiotoxicity, usually associated with increased oxidative stress, myofibrillar deterioration, and impaired cardiac contractile function, is a serious complication of antitumor therapy which may not be detected for many years. Growing evidence indicates that the regulation of cardiac microRNA (miRNA, miR) in response to exercise is essentially involved in the protective effect of exercise in the treatment of cardiovascular diseases. However, it is largely unknown whether and how exercise could prevent Dox-induced cardiotoxicity via regulating miRNA biology. In the current study, C57BL/6 mice were either subjected to a 3-week swimming program or remained sedentary. Mice were then treated with Dox (ip. 4 mg/kg/week for 4 weeks) to induce cardiotoxicity. Our data demonstrated that Dox resulted in marked reduction of cardiac ejection fraction (EF, %) and fractional shortening (FS, %) as measured by echocardiography. Interestingly, exercise significantly improved cardiac EF (%) and FS (%) in Dox-treated mice, indicating the protective effect of exercise in Dox-induced cardiotoxicity. Then, we performed microarray analysis (Affymetrix 3.0) showing that miR-27a-5p, miR-34b-3p, miR-185-3p, miR-203-3p, miR-669a-5p, miR-872-3p, and let-7i-3p were significantly reduced, while miR-2137 was increased in the hearts of exercised Dox-treated mice versus sedentary Dox-treated mice (FC(abs)>1.5, p<0.05). Using qRT-PCR, we further verified that miR-669a-5p was reduced by exercise training in Dox-treated mice. These data reveal that miR-669a-5p might be a potential miRNA mimicking the benefit of exercise in Dox-induced cardiotoxicity. Further study is needed to clarify the functional effect of miR-669a-5p and to identify its downstream target gene that contributes to the prevention and treatment of Dox-induced cardiotoxicity.

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83 DNP73 IS A DIRECT TARGET GENE OF BOTH GAIN-OF-FUNCTION BETA-CATENIN MUTANTS AND WILD-TYPE DEREGULATED BETA-CATENIN AND COUPLES WNT PATHWAY ACTIVATION TO CHEMIORESISTANCE IN HUMAN HCC

Journal of Hepatology ◽

10.1016/s0168-8278(08)60085-9 ◽

2008 ◽

Vol 48 ◽

pp. S36

Author(s):

V. Schinzari ◽

E. Palescandolo ◽

S. Vossio ◽

B. Testoni ◽

R. De iaco ◽

...

Keyword(s):

Wnt Pathway ◽

Target Gene ◽

Beta Catenin ◽

Wild Type ◽

Gain Of Function ◽

Pathway Activation ◽

Direct Target Gene ◽

Direct Target

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Regulation of a dpp target gene in the Drosophila embryo

Development ◽

10.1242/dev.124.2.303 ◽

1997 ◽

Vol 124 (2) ◽

pp. 303-311 ◽

Cited By ~ 3

Author(s):

J. Rusch ◽

M. Levine

Keyword(s):

Target Gene ◽

Fusion Gene ◽

Drosophila Embryo ◽

Specific Expression ◽

Downstream Target ◽

Embryonic Tissues ◽

Posterior Midgut ◽

Downstream Target Gene ◽

Genetic Epistasis ◽

Vp16 Fusion

In Drosophila, two TGF-beta growth factors, dpp and screw, function synergistically to subdivide the dorsal ectoderm into two embryonic tissues, the amnioserosa and dorsal epidermis. Previous studies have shown that peak dpp activity is required for the localized expression of zerknullt (zen), which encodes a homeodomain transcription factor. We present evidence that zen directly activates the amnioserosa-specific expression of a downstream target gene, Race (Related to angiotensin converting enzyme). A 533 bp enhancer from the Race promoter region is shown to mediate selective expression in the amnioserosa, as well as the anterior and posterior midgut rudiments. This enhancer contains three zen protein binding sites, and mutations in these sites virtually abolish the expression of an otherwise normal Race-lacZ fusion gene in the amnioserosa, but not in the gut. Genetic epistasis experiments suggest that zen is not the sole activator of Race, although a hyperactivated form of zen (a zen-VP16 fusion protein) can partially complement reduced levels of dpp activity. These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa.

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LncRNA ADAMTS9-AS2 in osteosarcoma inhibits cell proliferation and enhances paclitaxel sensitivity by suppressing microRNA-130a-5p

European Journal of Inflammation ◽

10.1177/2058739220934560 ◽

2020 ◽

Vol 18 ◽

pp. 205873922093456 ◽

Cited By ~ 1

Author(s):

Xiaoqiang Ren ◽

Jingwei Cai ◽

Yongheng Wang ◽

Xingren Zhu ◽

Jun Qian ◽

...

Keyword(s):

Cell Proliferation ◽

Noncoding Rna ◽

Target Gene ◽

Luciferase Reporter ◽

Critical Function ◽

Downstream Target ◽

Downstream Target Gene ◽

Proliferation Ability ◽

Polymerase Chain ◽

Qpcr Experiment

Introduction: Long noncoding RNA ADAMTS9-AS2 (lncRNA ADAMTS9-AS2) has critical function in tumor growth and drug resistance of various cancers. However, the role and mechanism of lncRNA ADAMTS9-AS2 in osteosarcoma (OS) is still unclear. Methods: The expression of lncRNA ADAMTS9-AS2 and MicroRNAs-130a-5p (miR-130a-5p) was detected by real-time polymerase chain reaction (RT-qPCR) experiment. In addition, we used the plasmids transfection to construct the lncRNA ADAMTS9-AS2 overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to paclitaxel (PTX) in OS cells upon up-regulating lncRNA ADAMTS9-AS2 expression were analyzed via CCK-8 assay, while Western blotting experiment was performed to detect the regulatory mechanism. Results: We found that lncRNA ADAMTS9-AS2 was down-regulated in OS tissues, and the OS patients with lncRNA ADAMTS9-AS2 downexprssion were usually accompanied with a poor prognosis. Subsequently, we discovered that up-regulation of lncRNA ADAMTS9-AS2 inhibited cell proliferation and increased the sensitivity to PTX in OS cells. Interestingly, the Western blot results showed that overexpression of lncRNA ADAMTS9-AS2 could lead to PTEN expression increased, with PI3K and p-AKT expression decreased, indicating that lncRNA ADAMTS9-AS2 could increase the OS cell sensitivity to PTX via regulating PTEN-PI3K/AKT pathway. Furthermore, we identified MicroRNAs-130a-5p (miR-130a-5p) as the downstream target gene of lncRNA ADAMTS9-AS2, which was further confirmed by the luciferase reporter assay. More importantly, our data revealed that miR-130a-5p mimics could partly reverse the influence on cell proliferation and drug sensitivity induced by lncRNA ADAMTS9-AS2 overexpression. Conclusion: LncRNA ADAMTS9-AS2 exerts its anti-carcinogenesis function by sponging miR-130a-5p, which might be a new therapeutic target for OS treatment.

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