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| Status |
Public on Nov 20, 2022 |
| Title |
N7-Methylguanosine tRNA modification promotes hepatocellular carcinoma metastasis after insufficient radiofrequency ablation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Radiofrequency heat ablation is an ideal radical cure for HCC treatment; however, insufficient radiofrequency ablation (IRFA) could lead to a high recurrence rate. N7-methylguanosine (m7G) on tRNAs is a heat-responding modification that is critical for yeast survival under high temperature, while its function and mechanism in HCC recurrence after IRFA are unknown. Here, we found that IRFA significantly up-regulates the level of m7G tRNA modification and its methyltransferase complex components METTL1 and WDR4 in multiple systems including HCC patient-derived xenograft (PDX) mouse, HCC tissues of patients, sublethal-heat-treated models of HCC cell lines and organoids. Functionally, gain- or loss-of function assays showed that METTL1 mediated m7G tRNA modification promotes HCC metastasis under sublethal heat exposure both in vitro and in vivo. Mechanistically, we found that METTL1 and m7G tRNA modification enhance the translation of SLUG and SNAIL in a codon frequency dependent manner under sublethal heat exposure. Overexpression of SLUG and SNAIL rescued the malignant potency of METTL1 knockdown HCC cells after sublethal heat stress. Our study uncovers the important physiological functions of m7G tRNA modification in heat stress responses and HCC recurrence after IRFA and suggests that targeting METTL1-m7G-SLUG and SNAIL axis could be a promising strategy to prevent HCC metastasis after radiofrequency heat ablation treatment.
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| Overall design |
Polyribosome associated mRNA sequencing was used to study the differential translated genes in METTL1 knockdown HCC cells with or without Heat treatment. TRAC-Seq was developed to identify the tRNA m7G methylome in the hepatocellular carcinoma cells with or without heat treatment.
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| Contributor(s) |
Zhu S, Kuang M |
| Citation(s) |
35965412 |
| BioProject |
PRJNA819155 |
| Submission date |
Apr 01, 2022 |
| Last update date |
Nov 20, 2022 |
| Contact name |
Shenghua Zhu |
| Organization name |
The First Affiliated Hospital, Sun Yat-sen University
|
| Street address |
58 Zhong Shan Road 2
|
| City |
Guangzhou |
| ZIP/Postal code |
510080 |
| Country |
China |
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| Platforms (2) |
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| Samples (18)
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| GSM5997599 |
Polysome-mRNA-seq-Huh7_Ctrl_Input_repeat 1 |
| GSM5997600 |
Polysome-mRNA-seq-Huh7_Ctrl_Input_repeat 2 |
| GSM5997601 |
Polysome-mRNA-seq-Huh7_Heat treated_Input_repeat 1 |
| GSM5997602 |
Polysome-mRNA-seq-Huh7_Heat treated_Input_repeat 2 |
| GSM5997603 |
Polysome-mRNA-seq-Huh7_Ctrl_repeat 1 |
| GSM5997604 |
Polysome-mRNA-seq-Huh7_Ctrl_repeat 2 |
| GSM5997605 |
Polysome-mRNA-seq-Huh7_Heat treated_repeat 1 |
| GSM5997606 |
Polysome-mRNA-seq-Huh7_Heat treated_repeat 2 |
| GSM5997607 |
Polysome-mRNA-seq-SNU449_NC_Input |
| GSM5997608 |
Polysome-mRNA-seq-SNU449_NC_Heat treated_Input |
| GSM5997609 |
Polysome-mRNA-seq-SNU449_shMETTL1_Heat treated_Input |
| GSM5997610 |
Polysome-mRNA-seq-SNU449_NC |
| GSM5997611 |
Polysome-mRNA-seq-SNU449_NC_Heat treated |
| GSM5997612 |
Polysome-mRNA-seq-SNU449_shMETTL1_Heat treated |
| GSM5997613 |
TRAC-Seq_MHCC97H_NC_Alkb_and_NaBH4_Treated |
| GSM5997614 |
TRAC-Seq_MHCC97H_NC_Alkb_Treated_Input |
| GSM5997615 |
TRAC-Seq_MHCC97H_NC_Heat treated_Alkb_and_NaBH4_treated |
| GSM5997616 |
TRAC-Seq_MHCC97H_NC_Heat treated_Alkb_Treated_Input |
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