BBOX1-AS1 mediates trophoblast cells dysfunction via regulating hnRNPK/GADD45A axis†

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Pathology

Background:

• Recurrent pregnancy loss (RPL) is a complex obstetric complication with unclear etiology.
• Trophoblast dysfunction is implicated in various pregnancy complications, including RPL.
• Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in pregnancy disorders, yet their specific involvement in RPL remains under-explored.

Purpose of the Study:

• To identify novel molecular players involved in trophoblast dysfunction in RPL.
• To investigate the role and mechanism of the lncRNA BBOX1-AS1 in the pathogenesis of RPL.

Main Methods:

• Quantitative real-time PCR to measure BBOX1-AS1 expression in villous tissues and serum from RPL patients and controls.
• In vitro functional assays (proliferation, migration, invasion, tube formation, apoptosis) using trophoblast cells with manipulated BBOX1-AS1 levels.
• Western blotting and qRT-PCR to assess signaling pathway activation (MAPK) and gene expression (GADD45A).
• RNA immunoprecipitation and Western blotting to investigate the interaction between BBOX1-AS1, hnRNPK, and GADD45A.

Main Results:

• BBOX1-AS1 was significantly upregulated in villous tissues and serum of RPL patients.
• Overexpression of BBOX1-AS1 inhibited trophoblast cell proliferation, migration, invasion, and tube formation, while promoting apoptosis.
• BBOX1-AS1 activated the p38 and JNK MAPK signaling pathways by upregulating GADD45A expression.
• BBOX1-AS1 enhanced GADD45A mRNA stability through binding to hnRNPK, leading to abnormal trophoblast function.

Conclusions:

• The novel lncRNA BBOX1-AS1 plays a critical role in trophoblast dysfunction associated with RPL.
• The BBOX1-AS1/hnRNPK/GADD45A axis is a key pathway contributing to RPL pathogenesis.
• BBOX1-AS1 represents a potential diagnostic biomarker and therapeutic target for RPL.