The multisystemic functions of FOXD1 in development and disease

Abstract

Transcription factors (TFs) participate in a wide range of cellular processes due to their inherent function as essential regulatory proteins. Their dysfunction has been linked to numerous human diseases. The forkhead box (FOX) family of TFs belongs to the "winged helix" superfamily, consisting of proteins sharing a related winged helix-turn-helix DNA-binding motif. FOX genes have been extensively present during vertebrates and invertebrates' evolution, participating in numerous molecular cascades and biological functions, such as embryonic development and organogenesis, cell cycle regulation, metabolism control, stem cell niche maintenance, signal transduction, and many others. FOXD1, a forkhead TF, has been related to different key biological processes such as kidney and retina development and embryo implantation. FOXD1 dysfunction has been linked to different pathologies, thereby constituting a diagnostic biomarker and a promising target for future therapies. This paper aims to present, for the first time, a comprehensive review of FOXD1's role in mouse development and human disease. Molecular, structural, and functional aspects of FOXD1 are presented in light of physiological and pathogenic conditions, including its role in human disease aetiology, such as cancer and recurrent pregnancy loss. Taken together, the information given here should enable a better understanding of FOXD1 function for basic science researchers and clinicians.

miR‐30a inhibits androgen‐independent growth of prostate cancer via targeting MYBL2, FOXD1, and SOX4

“…Our data also revealed that miR‐30a altered many cell cycle control genes to regulate AI cell growth. As key transcription factors, SOX4, MYBL2, and FOXD1 also play important roles in the cell cycle, which can transactivate some key cell cycle regulation genes, such as CCNB1, CCDN1, FOXM1, and MYC 34,35 . Here, we presented that SOX4, MYBL2, and FOXD1 may regulate many cell cycle control genes in PCa cell lines, such as CDC20, CCNB1, MDM2, and CDK4.…”

“…The miR‐30a negative‐relation genes in TCGA were filtered for miR‐30a targets predicted by “miRanda,” “TargetScan,” and “DIANA‐microT” programs (Figure 4A), and 15 TFs were further identified by intersecting with JASPARCORE (Vertebrata) transcription factors database (http://jaspar.genereg.net/) (Figure 4B). We selected FOXD1 and MYBL2 for further verification because of their role in promoting proliferation in different cancers 34,35 . The protein expression levels of MYBL2 and FOXD1 were significantly repressed by transfecting miR‐30a mimics and enhanced by transfecting miR‐30a inhibitor (Figure 4C).…”

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

“…The dysregulation of FOXD1 expression has previously been associated with malignant behavior in certain cancers and has been reported to contribute to aspects of tumor progression, such as drug resistance, metastasis, and stemness [11]. Aberrant FOXD1 mRNA expression was recognized as an independent marker in NSCLC patients [15].…”

“…FOXD1 is associated with cell programming, especially in renal and kidney development [7][8][9][10]. Abnormal FOXD1 expression is involved in the progression of tumors [11] including breast cancer [12], colorectal cancer, melanoma, glioma [13], osteosarcoma, renal cell carcinoma, ovarian carcinoma, medulloblastoma [14], and lung cancer [15]. Recently, clinical mRNA microarray data identified FOXD1 as a factor associated with poor prognosis and that is required for lung cancer cell proliferation [15].…”

“…FOXD1 overexpression is strongly associated with NSCLC proliferation and metastasis through the activation of vimentin [16]. Although several studies have tried to unravel the molecular networks of FOXD1 [11][12][13]16,17], the molecular mechanisms related to FOXD1 remain largely unexamined, especially in lung cancer.…”