Transcription factor c-fos induces the development of premature ovarian insufficiency by regulating MALAT1/miR-22-3p/STAT1 network

Abstract

Background The current study attempted to investigate the role of transcription factor c-fos in the development of premature ovarian insufficiency (POI) as well as the underlying mechanism involving the MALAT1/miR-22-3p/STAT1 ceRNA network. Methods Bioinformatics analysis was performed to extract POI-related microarray dataset for identifying the target genes. Interaction among c-fos, MALAT1, miR-22-3p, and STAT1 was analyzed. An in vivo POI mouse model was prepared followed by injection of sh-c-fos and sh-STAT1 lentiviruses. Besides, an in vitro POI cell model was constructed to study the regulatory roles of c-fos, MALAT1, miR-22-3p, and STAT1. Results c-fos, MALAT1, and STAT1 were highly expressed in ovarian tissues from POI mice and CTX-induced KGN cells, while miR-22-3p was poorly expressed. c-fos targeted MALAT1 and promoted MALAT1 transcription. MALAT1 competitively bound to miR-22-3p and miR-22-3p could suppress STAT1 expression. Mechanically, c-fos aggravated ovarian function impairment in POI mice and inhibited KGN cell proliferation through regulation of the MALAT1/miR-22-3p/STAT1 regulatory network. Conclusion Our findings highlighted inducing role of the transcription factor c-fos in POI through modulation of the MALAT1/miR-22-3p/STAT1 ceRNA network.

Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition

“…Currently, there is little known about the biological role also with molecular function of Lnc18q22.2. Due to the molecular mechanisms underlying transcription factor regulating lncRNA expression have been well documented in the past decade, 24 , 25 , 26 , 27 In light of the observed upregulation of Lnc18q22.2 in HCC cells under hypoxic conditions, our research endeavoured to ascertain whether this trend could be attributed to modulation by a transcription factor. Our findings reveal that the transcription factor KLF4 plays a pivotal role in the regulation of Lnc18q22.2 expression within HCC cells.…”