Oncotarget

Research Papers: Pathology:

Integrated analysis miRNA and mRNA profiling in patients with severe oligozoospermia reveals miR-34c-3p downregulates PLCXD3 expression

Zhiming Li, Zaozao Zheng, Jun Ruan, Zhi Li, Xuan Zhuang and Chi-Meng Tzeng _

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Oncotarget. 2016; 7:52781-52796. https://doi.org/10.18632/oncotarget.10947

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Abstract

Zhiming Li1,2, Zaozao Zheng1,2, Jun Ruan1,2, Zhi Li1,2, Xuan Zhuang4 and Chi-Meng Tzeng1,2,3

1 Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China

2 Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China

3 INNOVA Cell Theranostics/Clinics and TRANSLA Health Group, Xiamen University, Xiamen, Fujian, China

4 Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

Correspondence to:

Xuan Zhuang, email:

Chi-Meng Tzeng, email:

Keywords: global miRNA and mRNA profile; integrated analysis; miR-34c-3p; PLCXD3; spermatogenesis; Pathology Section

Received: June 06, 2016 Accepted: July 20, 2016 Published: July 29, 2016

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.


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