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Updated: Nov 10, 2025
Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
A regulatory loop among CD276, miR-29c-3p, and Myc exists in cancer cells against natural killer cell cytotoxicity
Chin-Cheng Lee1, Kuo-Hao Ho2, Tzu-Wen Huang3
1Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
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.
Insights
A novel regulatory loop involving cluster of differentiation 276 (CD276), Myc, and microRNA (miR)-29c-3p was identified. This pathway impacts cancer cell evasion of natural killer (NK) cell immunity, offering potential targets for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Immune checkpoints are crucial for regulating immune responses and preventing autoimmunity.
- While cancer immunotherapies have improved outcomes, not all patients respond effectively.
- Identifying novel immune checkpoints is vital for advancing cancer treatment.
Purpose of the Study:
- To explore the role of cluster of differentiation 276 (CD276), also known as B7H3, as a potential immune checkpoint in cancer.
- To elucidate the molecular mechanisms underlying CD276's function in the tumor microenvironment.
- To investigate the interplay between CD276, microRNAs, and oncogenic pathways in cancer progression.
Main Methods:
- Pan-cancer data analysis using The Cancer Genome Atlas (TCGA).
- Investigation of correlations between CD276 expression, natural killer (NK) cell infiltration, and microRNA levels.
- Gene set enrichment analyses to identify CD276-associated molecular pathways.
Main Results:
- CD276 was identified as a risk gene in multiple cancers and negatively correlated with NK cell cytotoxicity.
- A negative regulatory loop was found between CD276, Myc, and microRNA (miR)-29c-3p.
- CD276 overexpression suppressed miR-29c-3p, enhancing Myc activity and promoting cancer cell immune evasion.
- miR-29c-3p overexpression rescued CD276-impaired NK cell function.
Conclusions:
- A novel CD276-Myc-miR-29c-3p regulatory axis influences cancer cell resistance to NK cell-mediated killing.
- This pathway represents a potential therapeutic target for overcoming immune evasion in cancer immunotherapy.
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