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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 07, 2023 |
| Title |
PRMT1 inhibition activates the interferon pathway to potentiate antitumor immunity and enhance checkpoint blockade efficacy in melanoma |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyl transferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA (dsRNA) derived from endogenous retroviral elements (ERVs) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of DNMT1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8+T cells as well as IFNγ+CD8+T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB.
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| Overall design |
RNA-seq of control(CTRL), PRMT1-knockout B16-F10 cells(PRMT1 sg1) and control(shNC),PRMT1-konckdown A375 cells . ChIP-seq of H3K27 acetylation for control(CTRL) or PRMT1-knockout(PRMT1 sg1) B16-F10 cells.
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| Contributor(s) |
Tao H, Jin C, Zhou L, Deng Z, Li X, Dang W, Fan S, Li B, Ye F, Lu J, Kong X, Liu C, Luo C, Zhang Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 07, 2023 |
| Last update date |
Nov 08, 2023 |
| Contact name |
Liyuan Zhou |
| E-mail(s) |
zhouliyaun21@mails.ucas.ac.cn
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| Organization name |
University of Chinese Academy of Sciences
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| Street address |
国科大杭州高等研究院
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| City |
Hangzhou |
| State/province |
杭州市 |
| ZIP/Postal code |
310024 |
| Country |
China |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (20)
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| GSM7689124 |
B16_F10 cells, PRMT1_sg1,rep1 |
| GSM7689125 |
B16_F10 cells, PRMT1_sg1,rep2 |
| GSM7689126 |
B16_F10 cells, PRMT1_sg1,rep3 |
| GSM7689127 |
A375 cells, shNC,rep1 |
| GSM7689128 |
A375 cells, shNC,rep2 |
| GSM7689129 |
A375 cells, shNC,rep3 |
| GSM7689130 |
A375 cells, shPRMT1_1,rep1 |
| GSM7689131 |
A375 cells, shPRMT1_1,rep2 |
| GSM7689132 |
A375 cells, shPRMT1_1,rep3 |
| GSM7689133 |
B16_F10 cells, CTRL,H3K27ac, ChIP |
| GSM7689134 |
B16_F10 cells, CTRL_additional sequencing,H3K27ac, ChIP |
| GSM7689135 |
B16_F10 cells, PRMT1_sg1,H3K27ac, ChIP |
| GSM7689136 |
B16_F10 cells, PRMT1_sg1_additional sequencing,H3K27ac, ChIP |
| GSM7689137 |
B16_F10 cells, CTRL,Input |
| GSM7689138 |
B16_F10 cells, CTRL_additional sequencing,Input |
| GSM7689139 |
B16_F10 cells, PRMT1_sg1,Input |
| GSM7689140 |
B16_F10 cells, PRMT1_sg1_additional sequencing,Input |
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| Relations |
| BioProject |
PRJNA1003049 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240258_A375_shNC_shPRMT1.txt.gz |
3.5 Mb |
(ftp)(http) |
TXT |
| GSE240258_B16_F10_CTRL_PRMT1_sg1.txt.gz |
3.0 Mb |
(ftp)(http) |
TXT |
| GSE240258_RAW.tar |
479.9 Mb |
(http)(custom) |
TAR (of BW, GTF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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