Related Experiment Video
Updated: Feb 13, 2026
Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Novel biomarker ZCCHC13 revealed by integrating DNA methylation and mRNA expression data in non-obstructive
Zhiming Li1,2, Shuai Chen1, Yufeng Yang2
11Translational Medicine Research Center-Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian China.
Abstract:
The objective of this study was to identify genes regulated by methylation that were involved in spermatogenesis failure in non-obstructive azoospermia (NOA). Testis biopsies of patients with NOA and OA (with normal spermatogenesis) were evaluated by microarray analysis to examine DNA methylation and mRNA expression using our established integrative approach. Of the coordinately hypermethylated and down-regulated gene list, zinc-finger CCHC-type containing 13 (ZCCHC13) was present within the nuclei of germ cells of testicular tissues according immunohistochemistry, and there was decreased protein expression in men with NOA compared with OA controls. Mechanistic analyses indicated that ZCCHC13 increased c-MYC expression through the p-AKT and p-ERK pathways. To confirm the changes in ZCCHC13 expression in response to methylation, 5-aza-2'-deoxycitidine (5-Aza), a hypomethylating agent, was administered to mouse spermatogonia GC-1 cells. We demonstrated that 5-Aza enhanced protein and mRNA expression of ZCCHC13 epigenetically, which was accompanied by activation of p-AKT and p-ERK signaling. Our data, for the first time, demonstrate that ZCCHC13 is an important signaling molecule that positively regulates the AKT/MAPK/c-MYC pathway and that methylation aberrations of ZCCHC13 may cause defects in testis development in human disease, such as NOA.
Insights
Methylation changes in the ZCCHC13 gene are linked to spermatogenesis failure in non-obstructive azoospermia (NOA). Restoring ZCCHC13 expression may offer therapeutic potential for male infertility.
Area of Science:
- Reproductive Biology
- Epigenetics
- Molecular Genetics
Background:
- Non-obstructive azoospermia (NOA) is a major cause of male infertility, characterized by spermatogenesis failure.
- Aberrant DNA methylation is increasingly recognized as a factor contributing to reproductive disorders.
Purpose of the Study:
- To identify methylation-regulated genes involved in spermatogenesis failure in NOA.
- To investigate the role of zinc-finger CCHC-type containing 13 (ZCCHC13) in NOA pathogenesis.
Main Methods:
- Integrative analysis of DNA methylation and mRNA expression in testis biopsies from NOA and normozoospermic (OA) patients.
- Immunohistochemistry to assess ZCCHC13 protein localization and expression.
- In vitro experiments using 5-aza-2'-deoxycitidine (5-Aza) on mouse spermatogonia cells to study epigenetic regulation of ZCCHC13.
Main Results:
- ZCCHC13 was found to be coordinately hypermethylated and down-regulated in NOA patients.
- Decreased ZCCHC13 protein expression was observed in NOA testes.
- ZCCHC13 positively regulates c-MYC expression via the AKT/MAPK pathway, and 5-Aza treatment enhanced ZCCHC13 expression epigenetically.
Conclusions:
- Epigenetic aberrations in ZCCHC13 are implicated in the pathogenesis of non-obstructive azoospermia.
- ZCCHC13 acts as a key signaling molecule in the AKT/MAPK/c-MYC pathway, crucial for spermatogenesis.
- Targeting ZCCHC13 methylation may represent a novel therapeutic strategy for NOA.
More Related Videos
11:19Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 Kir4.1
Published on: September 26, 2015
06:28Vessel-Sparing Microsurgical Longitudinal Intussusception Vasoepididymostomy to Treat Epididymal Obstructive Azoospermia
Published on: May 27, 2022
Related Concept Videos
02:51mRNA Stability and Gene Expression
Cis-acting Elements involved in mRNA stability
02:51mRNA Stability and Gene Expression
01:42What is Gene Expression?
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
01:44Complementary DNA
02:22Regulated mRNA Transport
02:01pre-mRNA Processing
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...