TGF‐β1 regulates the lncRNA transcriptome of ovarian granulosa cells in a transcription activity‐dependent manner. Issue 1 (20th September 2022)

• Record Type: Journal Article
• Authors: Li, Qiqi; Huo, Yangan; Wang, Siqi; Yang, Liu; Li, Qifa; Du, Xing
• Is Part Of: Cell proliferation. Volume 56:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-20
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13336
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: Transforming growth factor β1 (TGF‐β1), an essential cytokine belongs to TGF‐β superfamily, is crucial for female fertility. Increasing evidence show that long noncoding RNAs (lncRNAs) influence the state of granulosa cells (GCs). This study aimed to detect the effects of TGF‐β1 on the lncRNA transcriptome, and investigate whether lncRNAs mediate the functions of TGF‐β1 in GCs. Material and Methods: RNA‐seq and bioinformatics analyses were performed to identify and characterize the differentially expressed lncRNAs (DElncRNAs). The regulatory mechanism of TGF‐β1 to lncRNA transcriptome was analyzed by chromatin immunoprecipitation. The effects of lncRNAs on the antiapoptotic and proproliferative functions of TGF‐β1 were examined by morphological analysis, fluorescence‐activated cell sorting, Cell Counting Kit‐8, and Western blot. Results: A total of 72 DElncRNAs highly sensitive to TGF‐β1 were identified with the criteria of |log2 (fold chage)| ≥ 3 and false discovery rate < 0.05. Functional assessment showed that DElncRNAs were enriched in TGF‐β, nuclear factor kappa B, p53, and Hippo pathways which are crucial for the normal state and function of GCs. Importantly, SMAD4 is essential for the regulation of TGF‐β1 to lncRNA transcriptome. In vitro studies confirmed that TGF‐β1 induced TEX14‐IT1 transcription in a SMAD4‐dependent manner, and TEX14‐IT1 mediated the antiapoptotic and proproliferative effects of TGF‐β1 in GCs. Conclusions: Our findings demonstrate that TGF‐β1 alters lncRNA transcriptome in a SMAD4‐dependent manner, and highlight that lncRNAs mediate the functions of TGF‐β1 in GCs, which contribute to a better understanding of the epigenetic regulation of female fertility. Abstract : The crosstalks between transforming growth factor β1 (TGF‐β1) and noncoding RNAs influence the normal states and functions of ovarian granulosa cells (GCs). RNA‐seq and bioinformatics analysis showed that TGF‐β1 regulates the long noncoding RNA (lncRNA) transcriptome of porcine GCs in a SMAD4‐dependent manner, which is also universal for the TGF‐β1‐induced transcriptomic alteration. In vitro studies confirmed that lncRNAs, such as TEX14‐IT1, mediated the antiapoptotic and proproliferative functions of TGF‐β1 in GCs. Our current study provides a panoramic view of lncRNA transcriptome and highlight the potential role of lncRNAs in mediating the biological functions of canonical TGF‐β signaling pathway, which contributes to a better understanding of the epigenetic regulation of female fertility.