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miR-34a/c induce caprine endometrial epithelial cell apoptosis by regulating circ-8073/CEP55 via the RAS/RAF/MEK/ERK

Xiaorui Liu1, Lei Zhang1, Lichun Yang1

  • 1College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.

Journal of Cellular Physiology
|June 1, 2020
PubMed

Insights

MicroRNAs (miRNAs) miR-34a and miR-34c induce caprine endometrial epithelial cell apoptosis by targeting circRNA8073 and centrosomal protein 55, impacting receptive endometrium establishment in dairy goats.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cellular Signaling

Background:

  • MicroRNAs (miRNAs) and circular RNAs (circRNAs) play crucial roles in mammalian endometrial receptivity and embryo implantation.
  • miR-34a and miR-34c are significantly expressed in the receptive endometrium of goats.
  • Understanding the molecular mechanisms regulating endometrial receptivity is vital for improving reproductive efficiency.

Purpose of the Study:

  • To investigate the functions and mechanisms of miR-34a/c in caprine endometrial epithelial cell (CEEC) apoptosis.
  • To elucidate the role of miR-34a/c in the establishment of receptive endometrium (RE) in dairy goats.
  • To explore the interaction between miR-34a/c, circRNA8073 (circ-8073), and centrosomal protein 55 (CEP55) in CEECs.

Main Methods:

  • Quantitative real-time PCR to assess miRNA and circRNA expression.
  • Western blotting to evaluate protein levels.
  • Luciferase reporter assays to confirm targeting interactions.
  • Cell apoptosis assays (e.g., TUNEL, Annexin V/PI staining).
  • Analysis of signaling pathways (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) and RE marker genes.

Main Results:

  • miR-34a/c were found to downregulate CEP55 expression in CEECs.
  • circ-8073 acted as a sponge for miR-34a/c, indicating a negative regulatory interaction.
  • miR-34a/c induced CEEC apoptosis by targeting circ-8073/CEP55, modulating the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
  • Complex feedback loops and cross-talk were observed between the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
  • miR-34a/c regulated key RE marker genes, including forkhead box M1, vascular endothelial growth factor, and osteopontin (OPN).

Conclusions:

  • miR-34a/c induce CEEC apoptosis through the circ-8073/CEP55 axis, impacting the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling cascades.
  • These miRNAs may play a significant role in regulating receptive endometrium establishment in dairy goats.
  • The findings provide insights into the molecular regulation of endometrial receptivity and potential targets for reproductive interventions.
Keywords:
CEP55apoptosiscaprine endometrial epithelial cellcirc-8073miR-34a/creceptive endometrium

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