miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells

Yang, Liu; Du, Xiaohong; Liu, Lu; Cao, Qiuyu; Pan, Zengxiang; Li, Qifa

doi:10.3390/cells8040298

Cited by 28 publications

(30 citation statements)

References 61 publications

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“…Furthermore, FACS revealed that FZD4 depletion significantly induced GC apoptosis ( Fig. 1h), indicating that FZD4, like its inducer SMAD4, is an antiapoptotic factor in porcine GCs 41 .…”

Section: Smad4 Is a Strong Inducer Of Fzd4 In Porcine Gcsmentioning

confidence: 90%

“…After incubation on ice for 30 min, the supernatant was collected by 12,000 × g centrifugation for 15 min at 4°C. The BCA Protein Assay Kit (#P0012, Beyotime, Jiangsu, China) was used to detect the concentration of total protein and western blotting was conducted as described previously 41 . Primary antibodies were anti-FZD4 (Sangon Biotech, #D121422, 1:1000), anti-β-catenin (Sangon Biotech, #D260137, 1:1000), anti-caspase-3/ cleaved caspase-3 (Proteintech, #19677-1-AP, 1:1000), and anti-GAPDH (ORIGENE, #TA802519, 1:5000).…”

Section: Western Blottingmentioning

confidence: 99%

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SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis

Yang

Liu

et al. 2020

Cell Death Dis

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The TGF-β and Wnt signaling pathways are interrelated in many cell types and tissues, and control cell functions in coordination. Here, we report that SMAD4, a downstream effector of the TGF-β signaling pathway, induces FZD4, a receptor of the Wnt signaling pathway, establishing a novel route of communication between these two pathways in granulosa cells (GCs). We found that SMAD4 is a strong inducer of FZD4, not only initiating FZD4 transcription but also activating FZD4-dependent Wnt signaling and GC apoptosis. Furthermore, we identified the direct and indirect mechanisms by which SMAD4 promotes expression of FZD4 in GCs. First, SMAD4 functions as a transcription factor to directly bind to the FZD4 promoter region to increase its transcriptional activity. Second, SMAD4 promotes production of SDNOR, a novel lncRNA that acts as a sponge for miR-29c, providing another mean to block miR-29c from degenerating FZD4 mRNA. Overall, our findings not only reveal a new channel of crosstalk between the TGF-β and Wnt signaling pathways, SMAD4-FZD4 axis, but also provide new insights into the regulatory network of GC apoptosis and follicular atresia. These RNA molecules, such as miR-29c and lnc-SDNOR, represent potential targets for treatment of reproductive diseases and improvement of female fertility.

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“…Furthermore, FACS revealed that FZD4 depletion significantly induced GC apoptosis ( Fig. 1h), indicating that FZD4, like its inducer SMAD4, is an antiapoptotic factor in porcine GCs 41 .…”

Section: Smad4 Is a Strong Inducer Of Fzd4 In Porcine Gcsmentioning

confidence: 90%

Section: Western Blottingmentioning

confidence: 99%

SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis

Yang

Liu

et al. 2020

Cell Death Dis

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“…Accumulating evidence has demonstrated that miRNAs are important endogenous regulators of gene expression, which have been investigated in various biological mechanisms [ 24 , 39 – 41 ]. However, with the increasing amounts of discovered lncRNAs, the function of very few lncRNAs has been characterized.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of lncRNA, miRNA and mRNA reveals novel insights into the fertility regulation of large white sows

Jia

et al. 2020

BMC Genomics

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Background Improving sow fertility is extremely important as it can lead to increased reproductive efficiency and thus profitability for swine producers. There are considerable differences in fertility rates among individual animals, but the underlying molecular mechanisms remain unclear. In this study, by using different types of RNA libraries, we investigated the complete transcriptome of ovarian tissue during the luteal (L) and follicular (F) phases of the estrous cycle in Large White pigs with high (H) and low (L) fecundity, and performed a comprehensive analysis of long noncoding RNAs (lncRNAs), mRNAs and micro RNAs (miRNAs) from 16 samples by combining RNA sequencing (RNA-seq) with bioinformatics. Results In total, 24,447 lncRNAs, 27,370 mRNAs, and 216 known miRNAs were identified in ovarian tissues. The genomic features of lncRNAs, such as length distribution and number of exons, were further analyzed. We selected a threshold of P < 0.05 and |log2 (fold change)| ≥ 1 to obtain the differentially expressed lncRNAs, miRNAs and mRNAs by pairwise comparison (LH vs. LL, FH vs. FL). Bioinformatics analysis of these differentially expressed RNAs revealed multiple significantly enriched pathways (P < 0.05) that were closely involved in the reproductive process, such as ovarian steroidogenesis, lysosome, steroid biosynthesis, and the estrogen and GnRH signaling pathways. Moreover, bioinformatics screening of differentially expressed miRNAs that share common miRNA response elements (MREs) with lncRNAs and their downstream mRNA targets were performed. Finally, we constructed lncRNA–miRNA–mRNA regulation networks. The key genes in these networks were verified by Reverse Transcription Real-time Quantitative PCR (RT-qRCR), which were consistent with the results from RNA-Seq data. Conclusions These results provide further insights into the fertility of pigs andcan contribute to further experimental investigation of the functions of these genes.

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“…While miR-1306 is encoded in most eukaryotic species, miR-3618 is restricted to primates (Merico et al, 2014). MiR-1306 targets F-box/Leucine rich repeat 5 (FBLX5), affecting epithelial to mesenchymal transitions and TGF beta-receptor 2, which is involved in the TGF-beta-SMAD4 signaling process ( Figure 2) (He et al, 2018;Yang et al, 2019). Other haploinsufficient miRNAs include miR-1286, selectively encoded in advanced primates, with in situ hybridization revealing its expression in the occipital cortex (Nowakowski et al, 2018).…”

Section: Digeorge Syndrome Critical Region 8 and Microrna Contributiomentioning

confidence: 99%

The Genetics and Epigenetics of 22q11.2 Deletion Syndrome

Morena

Oers

2020

Front. Genet.

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Chromosome 22q11.2 deletion syndrome (22q11.2del) is a complex, multi-organ disorder noted for its varying severity and penetrance among those affected. The clinical problems comprise congenital malformations; cardiac problems including outflow tract defects, hypoplasia of the thymus, hypoparathyroidism, and/or dysmorphic facial features. Additional clinical issues that can appear over time are autoimmunity, renal insufficiency, developmental delay, malignancy and neurological manifestations such as schizophrenia. The majority of individuals with 22q11.2del have a 3 Mb deletion of DNA on chromosome 22, leading to a haploinsufficiency of~106 genes, which comprise coding RNAs, noncoding RNAs, and pseudogenes. The consequent haploinsufficiency of many of the coding genes are well described, including the key roles of T-box Transcription Factor 1 (TBX1) and DiGeorge Critical Region 8 (DGCR8) in the clinical phenotypes. However, the haploinsufficiency of these genes alone cannot account for the tremendous variation in the severity and penetrance of the clinical complications among those affected. Recent RNA and DNA sequencing approaches are uncovering novel genetic and epigenetic differences among 22q11.2del patients that can influence disease severity. In this review, the role of coding and noncoding genes, including microRNAs (miRNA) and long noncoding RNAs (lncRNAs), will be discussed in relation to their bearing on 22q11.2del with an emphasis on TBX1.

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miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells

Cited by 28 publications

References 61 publications

SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis

SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis

Integrated analysis of lncRNA, miRNA and mRNA reveals novel insights into the fertility regulation of large white sows

The Genetics and Epigenetics of 22q11.2 Deletion Syndrome

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