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Deep-sequencing identification of differentially expressed miRNAs in decidua and villus of recurrent miscarriage patients.

Wang JM, Gu Y, Zhang Y, Yang Q, Zhang X, Yin L, Wang J - Arch. Gynecol. Obstet. (2016)

Bottom Line: In the decidual of RM patients, expression of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d were significantly up-regulated compared to normal pregnancy.In the villi of RM patients, expression of hsa-miR-100 and -146a-5p were significantly higher, while hsa-miR-1 and -372 were significantly lower compared to normal pregnancy.These data suggested that the pathogenic process of RM might be associated with the alteration of miRNAs expression profiles in decidua and villus.

View Article: PubMed Central - PubMed

Affiliation: The Second Hospital of Tianjin Medical University, Tianjin, China.

ABSTRACT

Purpose: MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in post-transcriptional gene expression regulation. The aim of this study was to identify differentially expressed miRNAs in decidua and villus of recurrent miscarriage (RM) patients.

Methods: Participants were recruited at the outpatient Department of Gynecology and Obstetrics, The Second Hospital of Tianjin Medical University, China. Decidua and villus tissues were collected by curettage from recruited RM patients and normal pregnant women with their informed consent. MiRNAs expression profiles in decidua or villus were respectively determined by the deep-sequencing analysis. The predicated target genes of these differentially expressed miRNAs were analyzed by miRWalk. The differential expressions of four miRNAs in decidua and four miRNAs in villus between the six pairs of RM patients and normal pregnant women were confirmed by qRT-PCR analysis. The expression patterns of two predicated target genes, Bcl-2 and Pten, in the same six pairs of decidual or villus tissues were detected by Western blotting analysis, respectively.

Results: Totally 18 RM patients and 15 normal pregnant women were recruited. Thirty-two miRNAs in decidua and four miRNAs in villus of RM patients were screened out to be significantly up-regulated compared to that of normal pregnant women, and five miRNAs in villus of RM patients were screened out to be remarkably down-regulated compared to that of normal pregnant women (P value < 0.05 and Fold change >2). These differentially expressed miRNAs were predicted to target a large number of genes that involved in cell apoptosis, p53 signaling pathway, cell cycle and other cellular bio-functions. Differential expressions of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d in decidua, as well as hsa-miR-1, -372, -100-5p and -146a-5p in villus, were validated by qRT-PCR analysis. In the decidual of RM patients, expression of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d were significantly up-regulated compared to normal pregnancy. In the villi of RM patients, expression of hsa-miR-100 and -146a-5p were significantly higher, while hsa-miR-1 and -372 were significantly lower compared to normal pregnancy. Furthermore, the expression of Bcl-2 and Pten, a predicated target gene of hsa-miR-1 or hsa-miR-372 respectively, was significantly up-regulated in the villi of RM patients.

Conclusions: These data suggested that the pathogenic process of RM might be associated with the alteration of miRNAs expression profiles in decidua and villus. Especially, the aberrant placental expression of hsa-miR-1 and -372 might be involved in the progression of RM, but need to be further investigated by larger studies in the future.

No MeSH data available.


Related in: MedlinePlus

Functional analyses of differentially expressed miRNA-predicted targets in decidua and villus. a/c Results of the GO analysis of the target genes predicted by differentially expressed miRNAs in deciduas (a) and villus (c). b/d Main biological processes of genes targeted by differentially expressed miRNAs in deciduas (b) and villus (d)
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Fig3: Functional analyses of differentially expressed miRNA-predicted targets in decidua and villus. a/c Results of the GO analysis of the target genes predicted by differentially expressed miRNAs in deciduas (a) and villus (c). b/d Main biological processes of genes targeted by differentially expressed miRNAs in deciduas (b) and villus (d)

Mentions: A total of 252 putative target mRNAs of 32 differentially expressed miRNAs in decidua, as well as 1281 putative target mRNAs of nine differentially expressed miRNAs in villus were predicted by miRWalk. The functions of predicted target genes and molecular pathways they potentially constitute were assessed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In decidua of RM patients, the predicted targets were significantly enriched for cell death, apoptosis, cell proliferation and response to hormone stimulus (Fig. 3a), which known to be participated in decidual development during embryo implantation. The pathway analysis showed that the predicted targets gene were involved in cancer, ErbB signaling pathway, focal adhesion and p53 signaling pathway, etc. (Fig. 3b). In the villus of RM patients, the predicted targets were significantly enriched for several biological processes known to be involved in embryonic or fetal development, such as cell proliferation, anti-apoptosis, blood vessel development (Fig. 3c). The pathway analysis showed that the predicted genes in villus were participated in apoptosis, p53-signaling pathway, cell cycle, et al. (Fig. 3d).Fig. 3


Deep-sequencing identification of differentially expressed miRNAs in decidua and villus of recurrent miscarriage patients.

Wang JM, Gu Y, Zhang Y, Yang Q, Zhang X, Yin L, Wang J - Arch. Gynecol. Obstet. (2016)

Functional analyses of differentially expressed miRNA-predicted targets in decidua and villus. a/c Results of the GO analysis of the target genes predicted by differentially expressed miRNAs in deciduas (a) and villus (c). b/d Main biological processes of genes targeted by differentially expressed miRNAs in deciduas (b) and villus (d)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4829624&req=5

Fig3: Functional analyses of differentially expressed miRNA-predicted targets in decidua and villus. a/c Results of the GO analysis of the target genes predicted by differentially expressed miRNAs in deciduas (a) and villus (c). b/d Main biological processes of genes targeted by differentially expressed miRNAs in deciduas (b) and villus (d)
Mentions: A total of 252 putative target mRNAs of 32 differentially expressed miRNAs in decidua, as well as 1281 putative target mRNAs of nine differentially expressed miRNAs in villus were predicted by miRWalk. The functions of predicted target genes and molecular pathways they potentially constitute were assessed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In decidua of RM patients, the predicted targets were significantly enriched for cell death, apoptosis, cell proliferation and response to hormone stimulus (Fig. 3a), which known to be participated in decidual development during embryo implantation. The pathway analysis showed that the predicted targets gene were involved in cancer, ErbB signaling pathway, focal adhesion and p53 signaling pathway, etc. (Fig. 3b). In the villus of RM patients, the predicted targets were significantly enriched for several biological processes known to be involved in embryonic or fetal development, such as cell proliferation, anti-apoptosis, blood vessel development (Fig. 3c). The pathway analysis showed that the predicted genes in villus were participated in apoptosis, p53-signaling pathway, cell cycle, et al. (Fig. 3d).Fig. 3

Bottom Line: In the decidual of RM patients, expression of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d were significantly up-regulated compared to normal pregnancy.In the villi of RM patients, expression of hsa-miR-100 and -146a-5p were significantly higher, while hsa-miR-1 and -372 were significantly lower compared to normal pregnancy.These data suggested that the pathogenic process of RM might be associated with the alteration of miRNAs expression profiles in decidua and villus.

View Article: PubMed Central - PubMed

Affiliation: The Second Hospital of Tianjin Medical University, Tianjin, China.

ABSTRACT

Purpose: MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in post-transcriptional gene expression regulation. The aim of this study was to identify differentially expressed miRNAs in decidua and villus of recurrent miscarriage (RM) patients.

Methods: Participants were recruited at the outpatient Department of Gynecology and Obstetrics, The Second Hospital of Tianjin Medical University, China. Decidua and villus tissues were collected by curettage from recruited RM patients and normal pregnant women with their informed consent. MiRNAs expression profiles in decidua or villus were respectively determined by the deep-sequencing analysis. The predicated target genes of these differentially expressed miRNAs were analyzed by miRWalk. The differential expressions of four miRNAs in decidua and four miRNAs in villus between the six pairs of RM patients and normal pregnant women were confirmed by qRT-PCR analysis. The expression patterns of two predicated target genes, Bcl-2 and Pten, in the same six pairs of decidual or villus tissues were detected by Western blotting analysis, respectively.

Results: Totally 18 RM patients and 15 normal pregnant women were recruited. Thirty-two miRNAs in decidua and four miRNAs in villus of RM patients were screened out to be significantly up-regulated compared to that of normal pregnant women, and five miRNAs in villus of RM patients were screened out to be remarkably down-regulated compared to that of normal pregnant women (P value < 0.05 and Fold change >2). These differentially expressed miRNAs were predicted to target a large number of genes that involved in cell apoptosis, p53 signaling pathway, cell cycle and other cellular bio-functions. Differential expressions of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d in decidua, as well as hsa-miR-1, -372, -100-5p and -146a-5p in villus, were validated by qRT-PCR analysis. In the decidual of RM patients, expression of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d were significantly up-regulated compared to normal pregnancy. In the villi of RM patients, expression of hsa-miR-100 and -146a-5p were significantly higher, while hsa-miR-1 and -372 were significantly lower compared to normal pregnancy. Furthermore, the expression of Bcl-2 and Pten, a predicated target gene of hsa-miR-1 or hsa-miR-372 respectively, was significantly up-regulated in the villi of RM patients.

Conclusions: These data suggested that the pathogenic process of RM might be associated with the alteration of miRNAs expression profiles in decidua and villus. Especially, the aberrant placental expression of hsa-miR-1 and -372 might be involved in the progression of RM, but need to be further investigated by larger studies in the future.

No MeSH data available.


Related in: MedlinePlus