4.7 Article

PSMC5 Promotes Proliferation and Metastasis of Colorectal Cancer by Activating Epithelial-Mesenchymal Transition Signaling and Modulating Immune Infiltrating Cells

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.657917

Keywords

colorectal cancer; metastasis; tumor infiltrated immune cells; PSMC5; m(6)A

Funding

  1. Guangci Distinguished Young Scholars Training Program from Ruijin Hospital [GCQN-2017-B09]
  2. Shanghai Jiao Tong University Science and Innovation Fund [YG2019QNB24]
  3. Shanghai Municipal Key Clinical Specialty [shslczdzk00102]

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The study revealed that overexpression of PSMC5 in CRC is associated with poor prognosis, with silencing leading to significant inhibition of cell proliferation and invasion. PSMC5 was found to regulate multiple pathways in CRC and its expression correlated with immune cell infiltration, making it a promising biomarker and target for immune therapy.
We designed the present study to access the roles and mechanisms of PSMC5 in colorectal cancer (CRC). Transcriptomic and clinical data from public datasets and our center were retrospectively analyzed. Functional assays were performed to investigate the effects of PSMC5 on CRC cells. The results showed that PSMC5 was significantly higher in cancer than normal tissues. Moreover, patients with higher expression of PSMC5 showed poorer prognosis. Silencing of PSMC5 dramatically suppressed the proliferation and invasion of CRC cells, while overexpression led to the opposite. In addition, we screened downstream targets and found that PSMC5 regulates multiple pathways including epithelial-mesenchymal transition, hypoxia, and immune response. Consistently, we found that PSMC5 was negatively correlated with levels of CD8 + T cells and B cells while promoting infiltration of macrophages and neutrophils. Collectively, these findings suggested that PSMC5 was a promising biomarker and target for immune therapy for CRC.

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