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LRWD1 expression is regulated through DNA methylation in human testicular embryonal carcinoma cells

  • Hung, Jui-Hsiang1
  • Cheng, Han-Yi2
  • Tsai, Yung-Chieh1
  • Pan, Hsien-An3
  • Omar, Hany A.4, 5
  • Chiu, Chien-Chih6
  • Su, Yin-Mei2
  • Lin, Yung-Ming7
  • Teng, Yen-Ni2
  • 1 Chia Nan University of Pharmacy and Science, Tainan, Taiwan , Tainan (Taiwan)
  • 2 National University of Tainan, No.33, Sec. 2, Shulin St., Tainan City, West Central District, 700, Taiwan , Tainan City (Taiwan)
  • 3 An-An Women and Children clinic, Tainan, Taiwan , Tainan (Taiwan)
  • 4 University of Sharjah, Sharjah, 27272, United Arab Emirates , Sharjah (United Arab Emirates)
  • 5 Beni-Suef University, Beni-Suef, 62514, Egypt , Beni-Suef (Egypt)
  • 6 Kaohsiung Medical University, Kaohsiung, Taiwan , Kaohsiung (Taiwan)
  • 7 University of British Columbia, Vancouver, British Columbia, Canada , Vancouver (Canada)
Published Article
Basic and Clinical Andrology
Springer (Biomed Central Ltd.)
Publication Date
May 20, 2021
DOI: 10.1186/s12610-021-00130-y
Springer Nature


BackgroundSperm growth and maturation are correlated with the expression levels of Leucine-rich repeat and WD repeat-containing protein 1 (LRWD1), a widely expressed protein in the human testicles. The decrease in LRWD1 cellular level was linked to the reduction in cell growth and mitosis and the rise in cell microtubule atrophy rates. Since DNA methylation has a major regulatory role in gene expression, this study aimed at exploring the effect of the modulation of DNA methylation on LRWD1 expression levels.ResultsThe results revealed the presence of a CpG island up of 298 bps (− 253 ~ + 45) upon LRWD1 promoter in NT2/D1 cells. The hypermethylation of the LRWD1 promoter was linked to a reduction in the transcription activity in NT2/D1 cells, as indicated by luciferase reporter assay. The methylation activator, floxuridine, confirmed the decrease in the LRWD1 promoter transcriptional activity. On the other hand, 5-Aza-2′-deoxycytidine (5-Aza-dc, methylation inhibitor), significantly augmented LRWD1 promoter activity and the expression levels of mRNA and proteins. Furthermore, DNA methylation status of LRWD1 promoter in human sperm genomic DNA samples was analyzed. The results indicated that methylation of LRWD1 promoter was correlated to sperm activity.ConclusionsThus, the regulation of LRWD1 expression is correlated with the methylation status of LRWD1 promoter, which played a significant role in the modulation of spermatogenesis, sperm motility, and vitality. Based on these results, the methylation status of LRWD1 promoter may serve as a novel molecular diagnostic marker or a therapeutic target in males’ infertility.

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