Biology subjects

Ihsan, A. U.

Publications and source records attributed to Ihsan, A. U..

4 recordsLinked to original sources

bioRxiv2026

SOCS1 expression in prostate epithelial cells is essential for tissue homeostasis and tumor suppression

Suppressor of cytokine signaling 1 (SOCS1) negative regulates inflammatory cytokine production and attenuates oncogenic growth factor signaling pathways. Reduced SOCS1 protein expression in human prostate cancer correlates with greater disease severity. To define the physiological functions of SOCS1 functions in the prostate, we conditionally ablated Socs1 in prostate epithelial cells of C57BL/6 mice. These Socs1{Delta}PE mice exhibited normal prostate development, maturation and lobular architecture. However, adult Socs1{Delta}PEmice developed progressive epithelial hyperplasia and inflammatory cell infiltration that were temporally and spatially distinct. SOCS1-deficient prostate showed increased epithelial cell proliferation and elevated oxidative stress markers, and prostate organoids recapitulated this hyperplasia phenotype. Diet-induced obesity exacerbated both hyperplasia and inflammation in SOCS1-deficient prostate. Upon transurethral infection with uropathogenic Escherichia coli UPEC1677 expressing the genotoxin colibactin, Socs1{Delta}PE mice developed invasive prostate cancer with complete loss of lobular architecture, whereas control mice developed hyperplasia and pre-neoplastic lesions. In vitro, SOCS1-deficient prostate organoid-derived epithelial cells exhibited increased DNA damage following exposure to UPEC1677. Deletion of the colibactin biosynthetic gene clbP in UPEC1677 abolished its ability to induce DNA damage in SOCS1-deficient cells and to drive prostate cancer in vivo. Proteomic analysis of prostate organoids revealed dysregulation of basal and luminal epithelial lineage markers and signaling pathway proteins that could promote neoplasia in SOCS1-deficient cells. Collectively, these findings establish an essential, epithelial cell-intrinsic role for SOCS1 in maintaining prostate tissue homeostasis by restraining proliferation, regulating lineage plasticity, limiting inflammation and oxidative stress, and conferring protection against genotoxic injury and neoplastic transformation.

cancer biology↗

bioRxiv2025

AAV-Mediated CAR-T therapy eradicate HIV reservoirs with augmented safety and persistence

Withdrawal statementThe authors have withdrawn their manuscript because additional studies are required to fully support the conclusions. These experiments are planned and a revision will be submitted in the future. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

bioengineering↗

bioRxiv2020

SILAC proteomics implicates the ubiquitin conjugating enzyme UBE2D in SOCS1-mediated downmodulation of the MET receptor in hepatocytes

Suppressor of Cytokine Signaling 1 (SOCS1) functions as a tumor suppressor in hepatocellular carcinoma (HCC) and many other types of cancers. SOCS1 mediates its functions by inhibiting tyrosine kinases, promoting ubiquitination and proteasomal degradation of signal transducing proteins, and by modulating transcription factors. Here, we studied the impact of SOCS1 on the hepatocyte proteome using Stable Isotopic Labelling of Amino acids in Cell culture (SILAC)-based mass spectrometry on the Hepa1-6 murine HCC cell line stably expressing wildtype SOCS1 or a mutant SOCS1 with impaired SH2 domain. As SOCS1 regulates the hepatocyte growth factor (HGF) receptor MET, the SILAC-labelled cells were stimulated or not with HGF. Following mass spectrometry analysis, differentially modulated proteins were identified, quantified and analyzed for pathway enrichment. Of the 3440 proteins identified in Hepa-SOCS1 cells at steady state, 181 proteins were significantly modulated compared to control cells. The SH2 domain mutation and HGF increased the number of differentially modulated proteins. Protein interaction network analysis revealed enrichment of SOCS1-modulated proteins within multiprotein complexes such as ubiquitin conjugating enzymes, proteasome, mRNA spliceosome, mRNA exosome and mitochondrial ribosome. These findings suggest that SOCS1, induced by cytokines, growth factors and diverse other stimuli, may dynamically modulate of large macromolecular regulatory complexes to help maintain cellular homeostasis. Notably, the expression of UBE2D ubiquitin conjugating enzyme, which is implicated in the control of growth factor receptor tyrosine kinase signaling, was found to be regulated by SOCS1.

molecular biology↗

bioRxiv2020

Prognostic significance of SOCS1 and SOCS3 tumor suppressors in hepatocellular carcinoma and its correlation to key oncogenic signaling pathways

Suppressor of cytokine signaling (SOCS) proteins SOCS1 and SOCS3 are considered tumor suppressors in liver hepatocellular carcinoma (LIHC). To gain insight into the underlying molecular mechanisms, the expression of SOCS1/ SOCS3 was evaluated in The Cancer Genome Atlas LIHC dataset along with key oncogenic signaling pathway genes. SOCS1 expression was not significantly reduced in HCC yet higher expression predicted favorable prognosis, whereas SOCS3 lacked predictive potential despite lower expression. Only a small proportion of the cell cycle, receptor tyrosine kinase, growth factor and RAS-RAF-MEK-MAPK signaling genes negatively correlated with SOCS1 or SOCS3, of which even fewer showed elevated expression in HCC and predicted survival. However, many PI3K-AKT-MTOR pathway genes showed mutual exclusivity with SOCS1/SOCS3 and displayed independent predictive ability. Among genes that negatively correlated with SOCS1/SOCS3, CDK2, MLST8, AURKA, MAP3K4 and RPTOR showed corresponding modulations in the livers of mice lacking Socs1 or Socs3 during liver regeneration and in experimental HCC, and in Hepa1-6 murine HCC cells overexpressing SOCS1/SOCS3. However, Cox proportional hazards model identified CXCL8, DAB2 and PIK3R1 as highly predictive in combination with SOCS1 or SOCS3. These data suggest that developing prognostic biomarkers and precision treatment strategies based on SOCS1/SOCS3 expression need careful testing in different patient cohorts.

cancer biology↗