ArticleOncogene2021
HuR up-regulates cell surface PD-L1 via stabilizing CMTM6 transcript in cancer.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- RNA‑binding proteins as epithelial transcriptome orchestrators in gastric cancer: Immune‑metabolic crosstalk and therapeutic vulnerability (Review).International journal of molecular medicine · 2026Review
- CircRNA-mediated regulation of immune checkpoints in lymphoma: a multidimensional network perspective.Frontiers in immunology · 2026Review
- Functional interplay between TTP/ZFP36 and HuR/ELAVL1 in cancer: a post-transcriptional regulatory network.Frontiers in oncology · 2026Review
- Inhibition of HuR/ELAVL-1 attenuates fibrotic progression in Mdx mice with dilated cardiomyopathy.Cellular and molecular life sciences : CMLS · 2025Article
- Integrated pan-cancer analysis of RNA binding protein HuR investigates its biomarker potential in prognosis, immunotherapy, and drug sensitivity.PLoS computational biology · 2025Article
- The Role of Tumor-Intrinsic HuR in Modeling the Pancreatic Tumor Microenvironment: Molecular Mechanisms and Therapeutic Opportunities.Molecular and cellular biology · 2025Review
- A PD-L1-Targeted Probe Cy5.5-A11 forACS omega · 2024Article
- Readers of RNA Modification in Cancer and Their Anticancer Inhibitors.Biomolecules · 2024Review
- Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy.RNA biology · 2024Review
- Targeting the RNA-Binding Protein HuR in Cancer.Cancer research · 2023Review
- Niclosamide improves cancer immunotherapy by modulating RNA-binding protein HuR-mediated PD-L1 signaling.Cell & bioscience · 2023Article
- Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis.Biology direct · 2023Article
- LncRNA CASC11 upregulation promotes HDAC4 to alleviate oxidized low-density lipoprotein-induced injury of cardiac microvascular endothelial cells.The Kaohsiung journal of medical sciences · 2023Article
- Small Molecules Targeting the RNA-Binding Protein HuR Inhibit Tumor Growth in Xenografts.Journal of medicinal chemistry · 2023Article
- Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner.Cancer immunology research · 2023Article
- Current Opinions on the Relationship Between CMTM Family and Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Review
- ExoPD-L1: an assistant for tumor progression and potential diagnostic marker.Frontiers in oncology · 2023Review
- CMTM6 as a master regulator of PD-L1.Cancer immunology, immunotherapy : CII · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the well-established role of CMTM6 in the stabilization of cell surface PD-L1 in cancer cells, the mechanisms underlying CMTM6 expression and regulation are still largely unknown. Here we unexpectedly find a strikingly positive correlation between CMTM6 and Hu-Antigen R (HuR) expression in most types of cancer. Mechanistically, we elucidate HuR stabilizes CMTM6 mRNA via direct association with AU-rich elements (AREs) in its 3'UTR and predominantly up-regulates CMTM6, which is readily abolished by HuR-specific inhibitor, MS-444. Phenotypically, we notice abundant cell surface PD-L1 in HuR-high cancer cells, which significantly inhibits immune activation of co-cultured T cells as indicated by IL-2 production. Treatment with MS-444 completely relieves immune suppression imposed by HuR-overexpression and further stimulates immune responses. Ectopic HuR accelerates allograft tumor progression in vivo, which is greatly compromised by simultaneous administration with MS-444. Our study uncovers a novel mechanism in control of CMTM6 and therefore PD-L1 expression, and suggests the potential of combining HuR inhibitor with PD-1/PD-L1 antibodies for cancer immunotherapy.
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