Hspb1
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB43979 | ENA |
REPOSITORIES: ENA
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Project description:Ovarian cancer has the worst prognosis in major gynecological cancers. Current therapies includes platinum, taxol, angiogenesis inhibitor, PARP inhibitor. However, most ovarian cancer patients develop resistance. Identification of more pro-tumor factors in ovarian cancer may shed insight into ovarian cancer biology and therapy. In this study, we find ZKSCAN3, a zinc-finger transcription factor is overexpressed in ovarian cancer. We show ZKSCAN3 promotes ovarian cancer cell proliferation. Through RNA-sequencing and ChIP-sequencing, HSPB1 is identified as a target gene of ZKSCAN3. HSPB1 expression is significantly decreased by suppressing ZKSCAN3. Suppressing HSPB1 expression inhibits ovarian cancer cell proliferation as well. In contrast, expressing exogenous HSPB1 partially rescues the cell proliferation in ZKSCAN3 knock-down cells. Collectively, our study uncovers a functional ZKSCAN3-HSPB1 axis that promotes ovarian cancer cell proliferation.
2025-11-12 | GSE248519 | GEO
Project description:Colorectal cancer (CRC) shows limited responsiveness to immune-checkpoint blockade, highlighting the need for further investigation. The intratumoral Treg/CD8⁺ T-cell ratio serves as a predictive biomarker for therapeutic efficacy. Here, we first demonstrate that targeting HSPB1 lowers this ratio and confers therapeutic benefit in CRC. Methods. Candidate genes were identified by integrative single-cell transcriptomics and spatial transcriptomics, followed by survival analyses of TCGA cohorts. Functional interrogation was performed using CRISPR-Cas9 engineered knockout cell lines. Subcutaneous tumor models were established, and the immune microenvironment was characterized by multiparametric flow cytometry. Mechanistic validation was achieved through bulk RNA-seq and complementary functional assays. Results. Single-cell profiling identified HSPB1 as a determinant of the intratumoral Treg/CD8⁺ T-cell ratio, and TCGA analysis showed its prognostic relevance in CRC. Spatial transcriptomics revealed colocalization of HSPB1-expressing tumor cells with Tregs. Subcutaneous tumor models demonstrated that CRISPR-mediated HSPB1 deletion or pharmacologic inhibition markedly suppressed tumor growth and reprogrammed the Treg-dominated microenvironment. In vitro polarization assays confirmed that targeting HSPB1 selectively restrains Treg differentiation without affecting Th17. Integrated transcriptomic and functional studies further elucidated that HSPB1 orchestrates CCL20–CCR6 mediated Treg recruitment, thereby shaping the immunosuppressive milieu within colorectal tumors.Conclusions. Targeting HSPB1 exerts dual anti-tumor effects by directly suppressing neoplastic proliferation and concurrently alleviating Treg-mediated immunosuppression within the tumor microenvironment.
2025-08-20 | GSE305561 | GEO
Project description:Mutations of the RNA-granule component TDRD7 (OMIM: 611258) cause pediatric cataract in humans. Here, we applied an integrated approach to elucidate the molecular pathology of cataract in Tdrd7 targeted-knockout (Tdrd7-/-) mice. Tdrd7-/- animals precipitously develop lens fiber cell abnormalities early in life, suggesting a global-level breakdown/mis-regulation of key cellular processes. High-throughput RNA-sequencing followed by iSyTE-integrated bioinformatics-based analysis identified the molecular chaperone and cytoskeletal-modulator, HSPB1 (HSP27), among the high-priority down-regulated candidates in Tdrd7-/- lens. Moreover, a protein 2-D fluorescence difference gel electrophoresis-coupled mass spectrometry screen also identified HSPB1 to be reduced in Tdrd7-/- lens, offering independent support for focusing efforts on this factor to explain Tdrd7-/- cataract. Reduction of HSPB1 preceded lens morphological abnormalities, suggesting that cytoskeletal defects underlie the Tdrd7-/- cataract phenotype. In agreement, scanning electron microscopy revealed abnormal fiber cell membrane protrusions in Tdrd7-/- lenses. Significantly, abnormal F-actin staining was detected specifically in Tdrd7-/- fiber cells that exhibit nuclear degradation, thereby revealing that there are distinct mechanisms based on pre- or post-nuclear degradation differentiation stage for F-actin cytoskeletal maintenance in fiber cells. Further, RNA-immunoprecipitation identified Hspb1 mRNA in wild-type lens lysate TDRD7-pulldowns, and single-molecule RNA-imaging showed co-localization of TDRD7 protein with cytoplasmic Hspb1 mRNA in a specific pre-nuclear degradation area of differentiating fiber cells, indicating that TDRD7-ribonucleoprotein complexes are necessary for controlling optimal levels of key factors in lens development. Together, these data uncover a novel role for TDRD7 in regulating elevation of stress-responsive chaperones for cytoskeletal maintenance in post-nuclear degradation lens fiber cells, perturbation of which causes early-onset cataracts.
2020-09-01 | GSE134384 | GEO
Project description:IP was performed to identify proteins interacting with HSPB1. Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and digested using an in-gel digestion protocol.
2025-03-07 | PXD050431 | JPOST Repository
Project description:ZKSCAN3 promotes ovarian cancer cell proliferation through upregulating HSPB1
| PRJNA1044418 | ENA
Project description:Trigeminal neuropathic pain (TNP) is one of the most debilitating forms of neuropathic pain, with its underlying mechanisms not yet fully understood. Urocortins (UCNs), a family of peptides within the corticotropin-releasing factor (CRF) family, have been implicated in various functions, including stress, anxiety, and social behaviors. In this study, we demonstrate that UCN1 in the trigeminal ganglion (TG) plays a pivotal role in partial infraorbital nerve transection (pIONT)-induced TNP in mice. pIONT induced UCN1 upregulation in large-diameter TG neurons, and silencing Ucn1 using siRNA or adeno-associated virus (AAV)-mediated shRNA effectively attenuated pIONT-induced orofacial mechanical allodynia. Furthermore, the transcription factor BTB-and-CNC homology 1 (BACH1) was identified as a direct regulator of Ucn1 expression, and knockdown of Bach1 reduced Ucn1 expression and alleviated pIONT-induced TNP. Mechanistically, pIONT increased the expression of corticotropin-releasing hormone receptor 1 (CRHR1), and intra-TG injection of UCN1 induced CRHR1-dependent mechanical allodynia, accompanied by activation of extracellular signal-regulated kinase (ERK) and cyclic-AMP responsive element binding protein (CREB), as well as upregulation of heat shock protein-1 (HSPB1). Finally, HSPB1, released from neurons via extracellular vesicles, activated satellite glial cells and macrophages through TLR2/TLR4 signaling, thereby promoting neuroinflammation. Collectively, our results suggest that BACH1-regulated UCN1 contributes to TNP by activating CRHR1/ERK/CREB/HSPB1 signaling pathway in the TG, and targeting this signaling axis may present a promising therapeutic strategy for TNP.
2026-08-05 | GSE342076 | GEO
Project description:Myocardial fibrosis is a major contributor to heart failure after myocardial infarction (MI), primarily driven by endothelial-to-mesenchymal transition (EndoMT). Heat shock protein B1 (HSPB1) has cardioprotective functions, but its role in MI-induced fibrosis remains unclear. Here, we show that cardiomyocyte-derived HSPB1 regulates the maturation and secretion of TGF-β1, thereby modulating endothelial phenotype and fibrotic remodeling. HSPB1 overexpression reduced fibrosis and preserved cardiac function, while its knockdown aggravated collagen deposition and EndoMT activation. Mechanistically, HSPB1 suppressed pro-TGF-β1 disulfide bond formation and secretion of mature TGF-β1, leading to decreased Smad2/3 phosphorylation and fibroblast activation. These findings identify HSPB1 as a redox-sensitive regulator that links cardiomyocyte homeostasis with endothelial transition, providing a potential therapeutic target for post-infarction myocardial fibrosis.
2025-12-22 | PXD072325 |
Project description:To analyze the role of HSP27 in bleomycin (BLM)-induced pulmonary fibrosis in vivo, we used TG mice that conventionally overexpressed HSP27. Our previously reported that HSP27 plays an important role in pulmonary fibrosis. In mice overexpressing HSPB1, BLM-induced fibrotic regions and collagen deposits were increased compared with those in control BL6 mice. Following intratracheal treatment of BLM, the HSP25 TG mice showed an abundance of mononuclear and neutrophils cells in the alveoli, greater destruction of alveolar septa, intra-alveolar hyaline membrane formation, and a marked increase in collagen deposition compared with control BL6 mice.
2023-11-20 | GSE233735 | GEO
Project description:Targeting HSPB1 Reduces Tumor Growth and Abrogates Treg-Mediated Tumor Immunosuppression
| PRJNA1306510 | ENA
Project description:GPX3 suppresses lung adenocarcinoma progression through HSPB1 ubiquitination and Hippo pathway activation
| PRJNA1504946 | ENA