Association of hsa-miR-145 overexpression in human testicular cells with male infertility

Zhang, Liyuan; Ding, Xianping; Nie, Shuangshuang; Li‐Ling, Jesse; Zhang, Yuping; Zhang, Hui; Chen, Lin; Ling-xiao, LI; Min, Di

doi:10.3892/mmr.2015.3273

Cited by 7 publications

(5 citation statements)

References 42 publications

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“…determined that miR-23b , miR-32 , miR-154 and miR-99 in MArrest and SCOS were up-regulated 42 , and we found that these genes were also up-regulated in NOA. SOX9 is an essential protein for the maturation of sertoli cells and normal spermatogenesis, and it is a possible target of miR-145 43 , 44 . Furthermore, we observed that mir-145 is one of the common up-regulated genes.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive functional enrichment analysis of male infertility

Razavi

Sabbaghian

Jalili

et al. 2017

Sci Rep

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Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome, transcriptome, and proteome to ensure the stability of the spermatogonia and supporting cells. The identification of signaling pathways linked to infertility has been hampered by the inherent complexity and multifactorial aspects of spermatogenesis. Systems biology is a promising approach to unveil underlying signaling pathways and genes and identify putative biomarkers. In this study, we analyzed thirteen microarray libraries of infertile humans and mice, and different classes of male infertility were compared using differentially expressed genes and functional enrichment analysis. We found regulatory processes, immune response, glutathione transferase and muscle tissue development to be among the most common biological processes in up-regulated genes, and genes involved in spermatogenesis were down-regulated in maturation arrest (MArrest) and oligospermia cases. We also observed the overexpression of genes involved in steroid metabolism in post-meiotic and meiotic arrest. Furthermore, we found that the infertile mouse model most similar to human MArrest was the Dazap1 mutant mouse. The results of this study could help elucidate features of infertility etiology and provide the basis for diagnostic markers.

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Section: Discussionmentioning

confidence: 99%

Comprehensive functional enrichment analysis of male infertility

Razavi

Sabbaghian

Jalili

et al. 2017

Sci Rep

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“…Although miRNAs are reported to regulate bone forming and resorption cells activities (58), circulating miRNA specific to bone metabolism has not been identified, owing to the diverse biologic roles and tissue distribution of miRNAs. As miR-145 has been detected in tissues other than bone, including human testicular cells and smooth muscle cells (59,60), it is reasonable to speculate that the circulating level of miR-145 is not solely related to bone metabolic status normal physiologic conditions. In this study, the negative correlation between circulating miR-145 and some bone turnover markers in AIS suggests that the abnormal systemic change of miR-145 in AIS osteoblasts and osteocytes may abrogate the physiologic profile of circulating miR-145 and other bone markers, therefore, leading to the unique correlation profile in AIS (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Aberrant miR‐145–5p/β‐catenin signal impairs osteocyte function in adolescent idiopathic scoliosis

et al. 2018

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Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and β-catenin mRNA ( CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active β-catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.-Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T. P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/β-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

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“…It was observed that overexpression of miR-145 downregulates expression of male sex-determining gene SOX9 that in turn induces male fertility. Therefore the oncogenic role of miR-145 reveals its diagnostics and prognostic value as an infertility bio-marker [51]. miR-1471 was found to be overexpressed in patients with sertoli-cell-only syndrome that is characterized by azoospermia therefore miR-1471 can be used as a promising strategy against male infertility [52].…”

Section: • Vol 17 • № 5 Obstetrics Gynecology and Reproductionmentioning

confidence: 99%

Identification of key miRNAs as regulatory biomarkers of gonadotropins leading to infertility in males

Oohayyed,

Mohammed,

Al-Rahim

et al. 2023

Akušerstvo, ginekologiâ i reprodukciâ

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Introduction. Infertility is a highly fatal reproductive system disorder that affects the ability of a couple to reproduce. Over the past decades, a drastic uplift has been recorded in infertility cases among males ranging from 20 to 70 % indicating spermatogenesis impairment.Aim: to identify key microRNAs (miRNAs) as regulatory biomarkers of gonadotropins involved in dysregulation of fertility-related genes to propose potential therapeutic strategies that would combat the action of oncogenic miRNAs (oncomiRs).Materials and Methods. Interaction analysis was performed between miRNAs and fertility-related genes namely luteinizing hormone choriogonadotropin receptor (LHCGR), gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR) and cystic fibrosis transmembrane conductance regulator (CFTR) to identify key miRNAs as regulatory biomarkers of gonadotropins leading to infertility in males.Results. A total of 10, 13, 31 and 18 strong and potential binding sites were predicted for miRNAs-LHCGR, miRNAs-GnRHR, miRNAs-FSHR, and miRNAs-CFTR respectively employing miRWalk (comprehensive genetic database including miRNA targets) followed by identification of 6, 18, 55 and 17 significant interactions through RNA22. Subsequently shortlisted miRNAs and messenger RNA (mRNA) regions were subjected to Vfold-Pipeline and RNAComposer individually for 3D structure prediction. Additionally molecular docking was carried out between miRNAs and mRNAs models that discovered potential and stable interactions elucidating miR-6880-FSHR(R2) as a highly stable complex with least binding affinity (-566.3) and high confidence score (0.999).Conclusion. Hence this study proposes key oncomiRs as a diagnostic biomarker and therapeutic target to bring about a promising treatment strategy against male factor infertility. However wet lab investigations are required for further validations of proposed study.

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Association of hsa-miR-145 overexpression in human testicular cells with male infertility

Cited by 7 publications

References 42 publications

Comprehensive functional enrichment analysis of male infertility

Comprehensive functional enrichment analysis of male infertility

Aberrant miR‐145–5p/β‐catenin signal impairs osteocyte function in adolescent idiopathic scoliosis

Identification of key miRNAs as regulatory biomarkers of gonadotropins leading to infertility in males

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