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The lncRNA LINC00339-encoded peptide promotes trophoblast adhesion to endometrial cells via MAPK and PI3K-Akt signaling pathways

  • Reproductive physiology and disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Background

Endometrial receptivity (ER), a pivotal event for successful embryo implantation, refers to the capacity of endometrium to allow the adhesion of the trophectoderm of the blastocyst to endometrial cells. In this paper, we set to elucidate whether the peptides encoded by lncRNAs could influence trophoblast cells’ adhesion to endometrial cells.

Methods

WGCNA construction and bioinformatics were used to find out the ER-related lncRNAs with coding potential. Protein analysis was done by immunoblotting and immunofluorescence (IF) microscopy. CCK-8 and Calcein-AM/PI double staining assays were employed to evaluate cell viability. The effect of the peptide on trophoblast spheroids’ adhesion to endometrial cells was evaluated. The RNA sequencing (RNA-seq) analysis was applied to identify downstream molecular processes.

Results

lncRNA LINC00339 was found to be related to ER development and it had been predicted to have protein-coding potential. LINC00339 had high occupancy of ribosomes and was confirmed to encode a 49-aa peptide (named LINC00339-205-49aa). LINC00339-205-49aa could promote the attachment of JAR trophoblast spheroids to Ishikawa endometrial cells in vitro. LINC00339-205-49aa also upregulated the expression of E-cadherin in Ishikawa cells. Mechanistically, MAPK and PI3K-Akt signaling pathways were involved in the modulation of LINC00339-205-49aa, which were activated by LINC00339-205-49aa in Ishikawa cells.

Conclusion

These data demonstrate that a previously uncharacterized peptide encoded by lncRNA LINC00339 has the ability to enhance JAR trophoblast spheroids’ adhesion to Ishikawa endometrial cells, highlighting a new opportunity for the development of drugs to improve ER.

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Funding

This work was supported by the Henan Province Crucial Research and Development and Promotion Projects (Tackling of Key Scientific and Technical Problems; Project number: 212102310048), the Henan Province Medical Science and Technology Research Program (Joint Co-construction; Project No.: LHGJ20210364), and the Doctoral Scientific Research Foundation of the Second Affiliated Hospital of Zhengzhou University (Project No.: 202104069).

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Authors and Affiliations

  1. Medical Research Center, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450014, People’s Republic of China

    Bo Zhou

  2. Department of Reproductive Medicine, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Road, Zhengzhou, 450014, Henan, China

    Guo Yu, Yan Li, Jing Li, Yungai Xiang, Lili Tong, Xiying Chu, Caiyi Wang & Yuxia Song

  3. Zhengzhou University, Zhengzhou, Henan, China

    Mingqi Zhao

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  1. Bo Zhou
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Highlights

1 LINC00339 can encode a 49-aa peptide.

2. LINC00339-205-49aa promotes JAR cells’ adhesion to Ishikawa cells.

3. MAPK and PI3K-Akt pathways are involved in the regulation of LINC00339-205-49aa.

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Zhou, B., Yu, G., Zhao, M. et al. The lncRNA LINC00339-encoded peptide promotes trophoblast adhesion to endometrial cells via MAPK and PI3K-Akt signaling pathways. J Assist Reprod Genet 41, 493–504 (2024). https://doi.org/10.1007/s10815-023-02995-6

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  • DOI: https://doi.org/10.1007/s10815-023-02995-6

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