Downregulation of KIF2C and TEKT2 is associated with male infertility and testicular carcinoma

Aging (Albany NY). 2021 Sep 30;13(19):22898-22911. doi: 10.18632/aging.203583. Epub 2021 Sep 30.

Abstract

Background: Genetic factors are important in spermatogenesis and fertility maintenance, and are potentially significant biomarkers for the early detection of infertility. However, further understanding of these biological processes is required.

Methods: In the present study, we sought to identify associated genes by reanalyzing separate studies from Gene Expression Omnibus datasets (GSE45885, GSE45887 and GSE9210) and validation datasets (GSE4797, 145467, 108886, 6872). The differential genes were used the limma package in R language. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by the clusterprofier package. The protein-protein interaction network was constructed by the STRING database. The interaction between mRNA and TF was predicted by miRWalk web. At last, The Cancer Genome Atlas data were used to identify hub gene expression levels in GEPIA web.

Results: The results showed that 27 shared genes associated with spermatogenesis. We effectively screen out two genes (KIF2C and TEKT2) and both validated by GSE4797, 145467, 108886 and 6872. Among 27 shared genes, KIF2C and TEKT2 both down-regulated in spermatogenesis. The network of TF-miRNA-target gene was established, we found KIF2C-miRNAs (has-miR-3154, 6075, 6760-5p, 1251-5p, 186-sp)-TFs (EP300, SP1) might work in spermatogenesis.

Conclusions: Our study might help to improve our understanding of the mechanisms in spermatogenesis and provide diagnostic biomarkers and therapeutics targets.

Keywords: azoospermia; bioinformatics; infertility; testis cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma / genetics*
  • Databases, Genetic
  • Gene Expression Regulation
  • Humans
  • Infertility, Male / genetics
  • Infertility, Male / metabolism*
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Male
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism*
  • Protein Array Analysis
  • Protein Interaction Maps
  • Testicular Neoplasms / genetics*

Substances

  • Biomarkers, Tumor
  • KIF2C protein, human
  • Microtubule Proteins
  • tektins
  • Kinesins