A regulatory loop among CD276, miR-29c-3p, and Myc exists in cancer cells against natural killer cell cytotoxicity

Chin Cheng Lee, Kuo Hao Ho, Tzu Wen Huang, Chwen Ming Shih, Shao Yuan Hsu, Ann Jeng Liu, Ku Chung Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Immune checkpoints regulate immunity to prevent autoimmunity and protect the host from damage during pathogenic infection. They also participate in subverting immune surveillance and promote antitumor immunity in cancers. Although immunotherapy improves clinical outcomes, not all cancer patients experience expected responses after therapy. Hence, it would be meaningful to explore crucial immune checkpoints in cancers for future immunotherapies. Methods and key findings: By analyzing pan-cancer data in The Cancer Genome Atlas (TCGA), cluster of differentiation 276 (CD276), also known as B7H3, was found to be a risk gene in several cancers. A positive correlation existed between CD276 and natural killer (NK) cell infiltration. Overexpression of CD276 attenuated NK cell-mediated cell killing. Furthermore, CD276 levels showed a significant negative association with microRNA (miR)-29c-3p. Overexpression of miR-29c-3p rescued CD276-reduced NK cell cytotoxicity. According to gene set enrichment analyses, CD276-associated genes were found to be enriched in genes that targeted Myc. A negative correlation existed between miR-29 expression and Myc activity. CD276 enhanced Myc phosphorylation levels while suppressing miR-29c-3p expression. In contrast, miR-29c-3p inhibited CD276 expression, leading to reduced Myc activity. Myc suppressed miR-29c-3p expression while promoting CD276 upregulation. Significance: These findings suggest that a negative regulatory loop among CD276, Myc, and miR-29c-3p influences cancer cells against NK cell cytotoxicity.

Original languageEnglish
Article number119438
JournalLife Sciences
Volume277
DOIs
Publication statusPublished - Jul 15 2021

Keywords

  • CD276 (B7H3)
  • Immune checkpoint
  • miR-29c-3p
  • Myc
  • NK cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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