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Zhimin Chen

Publications and source records attributed to Zhimin Chen.

3 recordsLinked to original sources
PubMed2026

OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization.

Gastric cancer remains a leading cause of cancer-related mortality worldwide, and the identification of clinically relevant biomarkers is critical for improving patient outcomes. Oxidized low-density lipoprotein receptor 1 (OLR1) has been implicated in tumor progression; however, its role in gastric cancer and the tumor microenvironment remains unclear. OLR1 expression and clinical significance were analyzed using The Cancer Genome Atlas (TCGA) dataset and validated in gastric cancer cell lines. Gain- and loss-of-function experiments, together with in vitro and in vivo assays, were performed to investigate the biological functions and underlying mechanisms of OLR1 in gastric cancer progression. OLR1 was significantly upregulated in gastric cancer and associated with unfavorable prognosis. Functional analyses demonstrated that OLR1 promoted gastric cancer cell proliferation, migration, and tumor growth. Mechanistically, OLR1 activated NF-κB signaling and facilitated macrophage polarization toward the M2 phenotype, thereby contributing to a protumorigenic microenvironment. OLR1 promotes gastric cancer progression through activation of NF-κB signaling and modulation of macrophage polarization. These findings identify OLR1 as a potential prognostic biomarker and therapeutic target for gastric cancer.

Humans↗
PubMed2024

Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during midembryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these two paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Animals↗
PubMed2024

Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during mid-embryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these 2 paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Preprint↗