title: Integrated analysis miRNA and mRNA profiling in patients with severe oligozoospermia reveals miR-34c-3p downregulates PLCXD3 expression.
abstract: Our previous research suggested that an integrated analysis of microRNA (miRNA) and messenger RNA (mRNA) expression is helpful to explore miRNA-mRNA interactions and to uncover the molecular mechanisms of male infertility. In this study, microarrays were used to compare the differences in the miRNA and mRNA expression profiles in the testicular tissues of severe oligozoospermia (SO) patients with obstructive azoospermia (OA) controls with normal spermatogenesis. Four miRNAs (miR-1246, miR-375, miR-410, and miR-758) and six mRNAs (SLC1A3, PRKAR2B, HYDIN, WDR65, PRDX1, and ADATMS5) were selected to validate the microarray data using quantitative real-time PCR. Using statistical calculations and bioinformatics predictions, we identified 33 differentially expressed miRNAs and 1,239 differentially expressed mRNAs, among which one potential miRNA-target gene pair, miR-34c-3p and PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), was identified. Immunohistochemical analysis indicated that PLCXD3 was located within the germ cells of the mouse and human testis. Moreover, we found that miR-34c-3p was able to decrease PLCXD3 expression in mouse (GC-1 and TM4) and human (NCM460) cell lines, presumably indicating the possibility that miR-34c-3p acts as an intracellular mediator in germinal lineage differentiation. Notably, we reported the expression of the PLCXD3 protein in a man with normal spermatogenesis and the lack of the PLCXD3 protein in a man with SO. Therefore, the identified miRNA and mRNA may represent a potentially novel molecular regulatory network and therapeutic targets for the study or treatment of SO, which might provide a better understanding of the molecular basis of spermatogenesis dysfunction.
authors.affiliation: Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China.|INNOVA Cell Theranostics/Clinics and TRANSLA Health Group, Xiamen University, Xiamen, Fujian, China.
authors.forename: Chi-Meng
authors.initials: CM
authors.lastname: Tzeng
mesh_terms: D000328:Adult; D000818:Animals; D053713:Azoospermia / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics* / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D055815:Young Adult
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D054801:Phosphoinositide Phospholipase C; C000607434:phosphatidylinositol specific phospholipase C, human
keywords: PLCXD3; Pathology Section; global miRNA and mRNA profile; integrated analysis; miR-34c-3p; spermatogenesis