| 2001 |
Prx2 (paired-related homeobox transcription factor) contains both activation and repression domains; the conserved PRX domain activates transcription, while the OAR (aristaless) domain inhibits transcription in a promoter- and cell-type-dependent manner. Deletion of the OAR domain results in a 20-fold increase in transcription from the tenascin reporter in NIH 3T3 cells but not in C2C12 cells. |
Transient transfection assays with truncation mutants, artificial promoters, and tenascin-c downstream target promoter |
DNA and cell biology |
Medium |
11244566
|
| 2001 |
Prx2 functions as a transcription factor that regulates the tenascin-C (TN-C) gene promoter in vascular smooth muscle cells; Prx2 is induced when SMCs are cultured on denatured collagen (simulating disrupted ECM), placing Prx2 downstream of changes in SMC-ECM interactions. |
In situ hybridization, transfection of SMC with Prx2 expression plasmid, TN-C promoter reporter assay, truncation analysis |
Circulation research |
Medium |
11463719
|
| 2003 |
Prx2 directly regulates Protease Nexin-1 (PN-1) gene expression: Prx2 binds to a cis element in the PN-1 promoter in vitro and activates the PN-1 promoter in transient transfection assays, increasing PN-1 expression at least fivefold upon Prx2 overexpression. |
Affymetrix GeneChip microarray, RT-PCR of stable transfectants, Northern blot, in vitro promoter binding (electrophoretic mobility shift), transient transfection reporter assay |
DNA and cell biology |
Medium |
12713735
|
| 2009 |
Prx2 (paired-related homeobox) was cloned as a pituitary transcription factor that binds the TAATT motif (identified by SELEX) and regulates the Fshb promoter in a cell-type-dependent manner: it activates Fshb promoter in CHO cells and represses it in pituitary LbetaT2 cells via the Fd2 and -596/-239 regions. |
Yeast one-hybrid cloning, RT-PCR, immunohistochemistry, transient transfection assay, electrophoretic mobility shift assay (EMSA), DNase I footprinting, SELEX |
The Journal of reproduction and development |
High |
19550106
|
| 1998 |
Prx1 and Prx2 double knockout mice show severe skeletal defects in craniofacial region, inner ear, and limbs not seen in single Prx2 knockouts, demonstrating that Prx1 and Prx2 function cooperatively and Prx2 partially compensates for Prx1 loss in skeletal morphogenesis. Prx2 inactivation alone produces no skeletal defects. |
Gene targeting (lacZ insertion knockout), histology, β-galactosidase activity detection, in situ hybridization for Fgf8 and Pax9 |
Development (Cambridge, England) |
High |
9729491
|
| 1999 |
Prx1 and Prx2 cooperatively maintain cell fates within craniofacial mesenchyme; double mutants show novel mandibular phenotypes including loss of distal mandibular arch structures, arrest of mandibular incisor, and absence of Meckel's cartilage. Cells within the hyoid arch take on first branchial arch properties, demonstrating a role for Prx1/Prx2 in cell fate maintenance. |
Compound mutant mouse generation (prx-1/prx-2 double knockout), lacZ fate mapping, in situ hybridization for pax9 and patched, transgenic cell marking |
Development (Cambridge, England) |
High |
9876178
|
| 2001 |
Prx1 and Prx2 are upstream regulators of sonic hedgehog (Shh) in the mandibular arch; loss of both Prx genes reduces Shh expression in oral epithelium adjacent to mandibular mesenchyme and decreases mesenchymal cell proliferation. Hedgehog pathway inhibition (jervine) partially phenocopies the Prx1/Prx2 double mutant jaw defects. |
Double knockout mice, in situ hybridization, pharmacological hedgehog pathway inhibition (jervine), cell proliferation analysis |
Development (Cambridge, England) |
High |
11532916
|
| 2000 |
Prx1 and Prx2 (homeobox transcription factors) are required for normal architecture of the great elastic arteries and ductus arteriosus; Prx1 single and Prx1/Prx2 double null mutants show abnormal aortic arch positioning and elongated ductus arteriosus, while Prx2 single mutants are viable without cardiovascular malformations, indicating Prx2 has a subordinate but additive role in vascular development. |
Gene-targeted knockout mice (Prx2-/-, Prx1-/-, Prx1/Prx2 double null), histology, vascular morphological analysis |
Virchows Archiv : an international journal of pathology |
High |
10664157
|
| 2003 |
PRX-2 (homeobox) regulates fetal fibroblast behaviors important for scarless wound healing: fibroblasts from Prx-2-/- mice show altered cellular proliferation, extracellular matrix reorganization, and reduced matrix metalloproteinase 2 and hyaluronic acid production compared to wild-type, but only in fetal (not adult) fibroblasts. |
Fibroblasts from Prx-2-/- knockout mice, RNase protection analysis, proliferation assays, ECM reorganization assays, MMP2 and hyaluronic acid measurements |
The Journal of investigative dermatology |
Medium |
12535210
|
| 2012 |
PRRX2 (paired-related homeobox) plays a role in proliferation of pituitary progenitor cells distinct from PRRX1: siRNA knockdown of Prx2 (but not Prx1) in TtT/GF pituitary cells induces p21 expression, indicating Prx2 regulates cell cycle via p21 in pituitary progenitors. |
siRNA knockdown in pituitary-derived cell line (TtT/GF), RT-PCR, immunohistochemistry with Ki67, co-localization studies with SOX2/PROP1 |
Journal of neuroendocrinology |
Medium |
22577874
|
| 2014 |
KLF6 specifically stimulates PRRX2 promoter activity and regulates Prrx2 expression in pituitary stem/progenitor cells; KLF6 directly binds to the Prrx2 promoter as confirmed by EMSA, and KLF6 and PRRX2 co-localize in SOX2-positive pituitary stem/progenitor cells. |
Promoter assay (co-transfection), siRNA interference, electrophoretic mobility shift assay (EMSA), immunohistochemistry |
The Journal of reproduction and development |
Medium |
24881871
|
| 2001 |
The Prx1 and Prx2 proteins differ in their transcription regulatory activities due to distinct carboxyl-terminal domains; Prx2 (which lacks the OAR inhibitory region found in Prx1a's carboxyl tail in a comparable functional context) shows differences in DNA binding affinity and transcriptional activation capacity, providing a mechanism for unequal compensation between Prx1 and Prx2 loci. |
Transient transfection assays with truncation mutants, DNA binding affinity measurements, artificial promoters and tenascin-c reporter |
The Journal of biological chemistry |
Medium |
11373278
|
| 2008 |
Expression of Prx1 and Prx2 in mandibular mesenchyme is regulated by signals from the mandibular epithelium: fibroblast growth factor (FGF) and hedgehog family members from epithelium positively regulate Prx gene expression, while endothelin-1 signaling from mesenchyme restricts Prx2 expression to the medial mandibular mesenchyme. |
Chick mandibular mesenchyme explant culture, epithelium removal/addition, pharmacological signaling pathway manipulation, in situ hybridization |
Developmental dynamics : an official publication of the American Association of Anatomists |
Medium |
18942149
|
| 2017 |
PRRX2 promotes epithelial-mesenchymal transition (EMT) and invasion in breast cancer; miR-212-5p suppresses TNBC invasion by targeting the 3'-UTR of PRRX2, and Prrx2 overexpression partially abrogates miR-212-5p-mediated suppression of migration/invasion and EMT markers (E-cadherin, vimentin). |
Luciferase reporter assay (3'-UTR targeting), Western blot, wound healing assay, Transwell invasion assay, miRNA overexpression |
Cellular physiology and biochemistry |
Medium |
29216628
|
| 2017 |
Silencing PRRX2 in breast cancer cells suppresses invasion, migration, and EMT by inhibiting Wnt/β-catenin signaling: PRRX2 knockdown prevents nuclear translocation of β-catenin and downregulates downstream Wnt targets; these effects occur in vitro and in vivo (xenograft). |
shRNA knockdown, Western blot, Transwell invasion/migration assay, xenograft mouse model, immunohistochemistry |
Cellular physiology and biochemistry |
Medium |
28750408
|
| 2019 |
PRRX2 inhibition suppresses colon cancer liver metastasis via inactivation of Wnt/β-catenin signaling: PRRX2 knockdown downregulates p-GSK3β, nuclear/cytoplasmic β-catenin, TCF4, and vimentin while upregulating E-cadherin; Wnt activator LiCl reverses these effects, placing PRRX2 upstream of Wnt/β-catenin in EMT regulation. |
siRNA and shRNA knockdown, Western blot, Transwell invasion/migration, liver metastasis mouse model, Wnt pathway activator rescue (LiCl) |
Pathology, research and practice |
Medium |
31471104
|
| 2021 |
PRRX2 acts as a transcription factor for IL-6 in hepatocellular carcinoma cells: CBS (cystathionine β-synthase)/H2S axis reduces PRRX2 expression, which in turn suppresses IL-6 transcription, inactivating the IL-6/STAT3 pathway and reducing Treg infiltration. |
CBS overexpression/knockout mice, HCC cell lines, Western blot, dual-luciferase/ChIP assays (implied by transcription factor designation), in vivo xenograft |
Journal for immunotherapy of cancer |
Medium |
34413167
|
| 2022 |
PRRX2 transcriptionally upregulates GCH1 (GTP cyclohydrolase 1), a ferroptosis suppressor, in glioblastoma stem cells; circLRFN5 binds to PRRX2 protein and promotes its degradation via ubiquitin-mediated proteasomal pathway, thereby reducing GCH1 expression and inducing ferroptosis. |
RNA immunoprecipitation (RIP), RNA pull-down, ubiquitination assay, dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), lentiviral overexpression/knockdown, BODIPY lipid peroxidation assay, xenograft |
Journal of experimental & clinical cancer research |
High |
36266731
|
| 2022 |
PRRX2 drives enzalutamide resistance in prostate cancer by activating CDK4/6/Rb/E2F and BCL2 pathways; identified via genome-wide CRISPR activation screen. CDK4/6 and BCL2 inhibitors sensitize PRRX2-expressing castration-resistant tumors to enzalutamide. |
Genome-wide CRISPR activation screen, gene expression analysis, pharmacological inhibition (CDK4/6i, BCL2i), in vivo tumor models |
Cancer research |
Medium |
35405009
|
| 2019 |
PRRX2 promotes fibroblast-to-neuron transdifferentiation resistance in adult human skin fibroblasts; PRRX2 is identified as a master regulator in the fibroblast Gene Regulatory Network whose knockdown, combined with HEY2 knockdown, significantly enhances transdifferentiation to induced neurons (MAP2+) when combined with ASCL1 overexpression and p53 shRNA. |
RNAseq of human fibroblast pairs during neuronal conversion, siRNA/shRNA knockdown of candidate genes, neuronal conversion assay (MAP2 staining) |
Biochemical and biophysical research communications |
Medium |
31255287
|
| 2023 |
Myoblast-derived exosomal PRRX2 directly binds the MIR22HG promoter to activate its transcription; elevated MIR22HG then sponges miR-128 to increase YAP1 nuclear translocation (Hippo pathway activation), thereby promoting osteogenic differentiation of BMSCs and attenuating osteoporosis in vivo. |
ChIP assay, dual-luciferase reporter assay, RIP assay, immunofluorescence (YAP1 nuclear translocation), Alizarin red/ALP osteogenic assay, ovariectomy osteoporosis mouse model |
Molecular medicine (Cambridge, Mass.) |
High |
37081396
|
| 2016 |
Uterine PRRX2 (homeobox transcription factor) restrains decidual differentiation of stromal cells by inhibiting lipolysis; Prx2 overexpression in uterine stromal cells decreases expression of adipocyte triglyceride lipase, leading to lipid droplet accumulation and reduced decidualization marker (Dtprp) expression. |
Adenovirus-mediated Prx2 overexpression in uterine stromal cells, in vivo and in vitro decidualization models, Western blot, immunohistochemistry, lipid droplet imaging |
Cell and tissue research |
Medium |
26987819
|
| 2024 |
PRRX2 directly regulates pannexin 3 (Panx3) expression in preodontoblasts: Prrx2 overexpression activates the Panx3 promoter in luciferase reporter assays, protein-DNA complex formation is confirmed by EMSA, and Prrx2 siRNA knockdown inhibits Panx3 expression. |
In situ hybridization (tooth sections), dual-luciferase reporter assay, EMSA, siRNA knockdown |
Journal of oral biosciences |
Medium |
39733924
|
| 2025 |
PRRX2 directly binds to the ATOX1 promoter and transcriptionally activates ATOX1 expression in hepatocellular carcinoma cells; PRRX2 knockdown reduces ATOX1 expression, inhibits cell proliferation, invasion, EMT, and promotes cuproptosis. |
JASPAR database prediction of binding sites, ChIP or direct promoter binding assays, siRNA knockdown, Western blot, xenograft model |
Cellular signalling |
Medium |
40393577
|
| 2025 |
PRRX2 directly binds the CNTN3 promoter and transcriptionally activates CNTN3 expression in colorectal cancer cells, promoting EMT and metastasis; PRRX2 knockdown reduces CNTN3 expression and reverses EMT marker alterations. |
Chromatin immunoprecipitation (ChIP), dual-luciferase assay, siRNA knockdown, Western blot, xenograft model |
Cell division |
Medium |
41882765
|
| 2025 |
PRRX2 directly enhances GLI2 transcription, activating the hedgehog pathway to inhibit tumor cell senescence and promote pancreatic cancer proliferation, invasion, and metastasis; hedgehog pathway inhibitors or GLI2 silencing partially reverse PRRX2-driven effects. |
PRRX2 knockdown/overexpression, senescence assays, ChIP or promoter binding (implied by 'directly enhanced transcription'), hedgehog inhibitor treatment, GLI2 siRNA epistasis |
Cancer science |
Medium |
40619170
|
| 2024 |
Upregulation of PRRX2 in irradiated skin cells (via Marveld3 silencing) reduces intracellular Fe2+ and ROS levels and suppresses lipid peroxidation, functioning as a stress-responsive mechanism to counteract radiation-induced ferroptosis. |
siRNA silencing of Marveld3, PRRX2 overexpression plasmid, MDA/Fe2+/ROS assays, BODIPY staining, RNA sequencing, immunohistochemistry in rat skin |
Molecular medicine (Cambridge, Mass.) |
Medium |
39434056
|
| 2009 |
Prx1 and Prx2 regulate cell survival, region-specific chondrogenesis, and osteogenesis during mandibular morphogenesis; Prx1/Prx2 double mutants show growth abnormalities in mandibular processes from E10.5, loss of eHand-expressing mesenchyme subpopulation, failure of Meckel's cartilage chondrogenesis, and accelerated ossification causing mandibular process fusion. |
Prx1/Prx2 double knockout mice, histological analysis, in situ hybridization (eHand and chondrogenic markers), cell survival assays |
Developmental dynamics : an official publication of the American Association of Anatomists |
Medium |
19777594
|