This review centers on the pivotal role of the oncoprotein FOSL1, within the dimeric AP-1 transcription factor consisting of FOS-related elements. FOSL1 emerges as a key regulator governing invasion and metastatic dissemination, therefore making it a promising target for therapeutic intervention in cancer patients. The review provides a comprehensive survey of the regulatory mechanisms that exert influence over FOSL1. These encompass a spectrum of transcriptional and post-translational modifications. Notably, we unveiled the intricate involvement of diverse non-coding RNAs, specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the modulation of FOSL1 expression through targeted interactions with its mRNA transcripts. Furthermore, an exploration into the functional dimensions of FOSL1 unfolds, encompassing apoptosis, proliferation, and migration. This investigation is accompanied by a thorough examination of the elaborate signaling pathways that underpin these multifaced roles. Additionally, emphasis is placed on the role of FOSL1 in orchestrating the stimulation of various cytokines, including TGF-beta, and the initiation of IL-6 and VEGF production in tumor-associated macrophages (TAMs) that transverse into the tumor microenvironment. A distinct focus is dedicated to appraising the prognostic implications associated with FOSL1. Finally, insights emerge into the evolving roles of FOSL1 in the context of mechanisms governing resistance and dependency on targeted therapeutic modalities.

Only two percent of Glioblastoma multiforme (GBM) patients respond to standard care and survive beyond 36 months (long-term survivors, LTS) while the majority survive less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that characterize aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the GO-categories “epithelial to mesenchymal transition” and “response to hypoxia”. In this paper we applied upstream analysis approach which involves state-of-art promoter analysis and network analysis of the dysregulated genes potentially responsible for short survival in GBM. Binding sites for transcription factors associated with GBM pathology like NANOG, NF-κB, REST, FRA-1, PPARG and seven others were found enriched in the promoters of the dysregulated genes. We reconstructed the gene regulatory network with several positive feedback loops controlled by five master regulators – IGFBP2, VEGFA, VEGF165, PDGFA, AEBP1 and OSMR which can be proposed as biomarkers and as therapeutic targets for enhancing GBM prognosis. Critical analysis of this gene regulatory network gives insights on mechanism of gene regulation by IGFBP2 via several transcription factors including the key molecule of GBM tumor invasiveness and progression, FRA-1. All the observations are validated in independent cohorts and their impact on overall survival is studied.