Gene Expression Profiling of Peri-Implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway In Vivo

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

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Gene expression profiling of in vivo UVB-irradiated human epidermis

Photodermatology Photoimmunology & Photomedicine ◽

10.1111/j.1600-0781.2004.00097.x ◽

2004 ◽

Vol 20 (3) ◽

pp. 129-137 ◽

Cited By ~ 25

Author(s):

Claes D. Enk ◽

Iris Shahar ◽

Ninette Amariglio ◽

Gideon Rechavi ◽

Naftali Kaminski ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Human Epidermis

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Targeting histone methyltransferase G9a inhibits growth and Wnt signaling pathway by epigenetically regulating HP1α and APC2 gene expression in non-small cell lung cancer

Molecular Cancer ◽

10.1186/s12943-018-0896-8 ◽

2018 ◽

Vol 17 (1) ◽

Cited By ~ 20

Author(s):

Keqiang Zhang ◽

Jinhui Wang ◽

Lu Yang ◽

Yate-Ching Yuan ◽

Tommy R. Tong ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Wnt Signaling Pathway ◽

Histone Methyltransferase ◽

Small Cell ◽

Small Cell Lung

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The microRNA miR-8 is a conserved negative regulator of Wnt signaling

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0807763105 ◽

2008 ◽

Vol 105 (40) ◽

pp. 15417-15422 ◽

Cited By ~ 130

Author(s):

Jennifer A. Kennell ◽

Isabelle Gerin ◽

Ormond A. MacDougald ◽

Ken M. Cadigan

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Target Genes ◽

Wnt Signaling Pathway ◽

Negative Regulator ◽

Animal Development ◽

Protein Levels ◽

Evolutionarily Conserved ◽

Multiple Levels

Wnt signaling plays many important roles in animal development. This evolutionarily conserved signaling pathway is highly regulated at all levels. To identify regulators of the Wnt/Wingless (Wg) pathway, we performed a genetic screen in Drosophila. We identified the microRNA miR-8 as an inhibitor of Wg signaling. Expression of miR-8 potently antagonizes Wg signaling in vivo, in part by directly targeting wntless, a gene required for Wg secretion. In addition, miR-8 inhibits the pathway downstream of the Wg signal by repressing TCF protein levels. Another positive regulator of the pathway, CG32767, is also targeted by miR-8. Our data suggest that miR-8 potently antagonizes the Wg pathway at multiple levels, from secretion of the ligand to transcription of target genes. In addition, mammalian homologues of miR-8 promote adipogenesis of marrow stromal cells by inhibiting Wnt signaling. These findings indicate that miR-8 family members play an evolutionarily conserved role in regulating the Wnt signaling pathway.

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Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo

Molecular Medicine Reports ◽

10.3892/mmr.2015.4586 ◽

2015 ◽

Vol 13 (1) ◽

pp. 720-730 ◽

Cited By ~ 8

Author(s):

LIPING OU ◽

LIAOQIONG FANG ◽

HEJING TANG ◽

HAI QIAO ◽

XIAOMEI ZHANG ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells

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Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0328-x ◽

2019 ◽

Vol 51 (11) ◽

pp. 1-20 ◽

Cited By ~ 2

Author(s):

Jun-Cheng Guo ◽

Yi-Jun Yang ◽

Jin-Fang Zheng ◽

Jian-Quan Zhang ◽

Min Guo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Stem Cell ◽

Wnt Signaling ◽

Signaling Pathway ◽

Methylation Level ◽

Wnt Signaling Pathway ◽

The Self ◽

Self Renewal

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

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