<p>Cryptorchidism, a major reproductive malformation in dogs, is associated with an increased risk of testicular cancer. In this study, we aimed to compare miRNA expression and 3′UTR length variation in the mRNAs of differentially expressed genes (DEGs) between undescended (UD) and descended (D) canine testes without signs of tumorigenesis. In total, expression of 453 miRNA genes was detected, and over 100 miRNA DEGs were identified in the UD vs. D and UD vs. C (control) comparisons. Predicted target sequences for DEG miRNAs were in silico identified in numerous mRNAs, including 12 of 19 a priori selected genes related to testicular cancer. In silico analysis of miRNA and mRNA DEGs revealed that some of target mRNAs showed significant differences in UD and D/C testes and approximately 50% of miRNA–mRNA pairs exhibited an inverse expression pattern, including cancer-related genes (e.g., <i>AR</i>,<i> IGF1R</i>,<i> KIT</i>,<i> KITLG</i>,<i> SALL4</i>, and <i>SPRY4</i>). Analysis of the 3′UTR length of DEG mRNAs identified 962 transcripts with altered 3′UTR length in both the UD vs. D and UD vs. C comparisons. 3′UTR lengthening (e.g., in cancer-related genes such as <i>LATS2</i>,<i> SRPK2</i>, and <i>AKT3</i>) was the most common alteration observed. Our findings provide a new insight into molecular alterations associated with canine cryptorchidism. We suggest that in undescended canine testes without signs of tumorigenesis dysregulated expression of protein-coding genes, including candidate cancer-associated genes, can be associated with altered expression of specific miRNAs, as well as variations in the 3′UTR length of certain target DEG mRNAs.</p>

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Dysregulation of miRNA expression and 3′UTR length variation in target mRNAs in the testes of dogs with cryptorchidism

  • Joanna Nowacka-Woszuk,
  • Arkadiusz Kajdasz,
  • Monika Stachowiak,
  • Izabela Szczerbal,
  • Marek Switonski

摘要

Cryptorchidism, a major reproductive malformation in dogs, is associated with an increased risk of testicular cancer. In this study, we aimed to compare miRNA expression and 3′UTR length variation in the mRNAs of differentially expressed genes (DEGs) between undescended (UD) and descended (D) canine testes without signs of tumorigenesis. In total, expression of 453 miRNA genes was detected, and over 100 miRNA DEGs were identified in the UD vs. D and UD vs. C (control) comparisons. Predicted target sequences for DEG miRNAs were in silico identified in numerous mRNAs, including 12 of 19 a priori selected genes related to testicular cancer. In silico analysis of miRNA and mRNA DEGs revealed that some of target mRNAs showed significant differences in UD and D/C testes and approximately 50% of miRNA–mRNA pairs exhibited an inverse expression pattern, including cancer-related genes (e.g., AR, IGF1R, KIT, KITLG, SALL4, and SPRY4). Analysis of the 3′UTR length of DEG mRNAs identified 962 transcripts with altered 3′UTR length in both the UD vs. D and UD vs. C comparisons. 3′UTR lengthening (e.g., in cancer-related genes such as LATS2, SRPK2, and AKT3) was the most common alteration observed. Our findings provide a new insight into molecular alterations associated with canine cryptorchidism. We suggest that in undescended canine testes without signs of tumorigenesis dysregulated expression of protein-coding genes, including candidate cancer-associated genes, can be associated with altered expression of specific miRNAs, as well as variations in the 3′UTR length of certain target DEG mRNAs.