NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA
ABSTRACT Background 5‐methylcytosine (m5C) methylation is the crucial posttranscriptional modification of RNA. NSUN4, a methyltransferase for m5C methylation, contributes to lung tumorigenesis. Here, we determined the precise action of NSUN4 on the development of non‐small cell lung cancer (NSCLC)....
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-03-01
|
| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.70023 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850051219840565248 |
|---|---|
| author | Zhilong Li Xianzhen Wu |
| author_facet | Zhilong Li Xianzhen Wu |
| author_sort | Zhilong Li |
| collection | DOAJ |
| description | ABSTRACT Background 5‐methylcytosine (m5C) methylation is the crucial posttranscriptional modification of RNA. NSUN4, a methyltransferase for m5C methylation, contributes to lung tumorigenesis. Here, we determined the precise action of NSUN4 on the development of non‐small cell lung cancer (NSCLC). Methods NSUN4 and CDC20 mRNA expression was detected by quantitative PCR. Western blot and immunohistochemistry were used for the analysis of protein expression. Cell growth, apoptosis, invasiveness, migratory ability, and stemness potential were evaluated by colony formation, flow cytometry, transwell, and sphere formation assays. The influence of NSUN4 in CDC20 mRNA was analyzed using RNA immunoprecipitation (RIP) assay and Actinomycin D (Act D) treatment. Subcutaneous xenograft studies were performed to analyze the function in vivo. Results In human NSCLC tumors and cell lines, NSUN4 and CDC20 levels were upregulated. NSUN4 inhibition diminished NSCLC cell growth, stemness, invasiveness, and migratory ability in vitro, while NSUN4 increase had opposite effects. A positive expression association between CDC20 and NSUN4 was observed in NSCLC samples. Mechanistically, NSUN4 enhanced the stability of CDC20 mRNA through m5C modification. CDC20 depletion significantly counteracted NSUN4‐driven cell phenotype alterations in vitro. Additionally, inhibition of NSUN4 impeded the growth of A549 NSCLC subcutaneous xenografts in vivo. Conclusion Our findings identify the pro‐tumorigenic property of the NSUN4/CDC20 cascade in NSCLC. Targeting the novel cascade may be a promising way for combating this deadly disease. |
| format | Article |
| id | doaj-art-9407b15a33ca4306bf2e9b0d929149a0 |
| institution | DOAJ |
| issn | 1759-7706 1759-7714 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj-art-9407b15a33ca4306bf2e9b0d929149a02025-08-20T02:53:13ZengWileyThoracic Cancer1759-77061759-77142025-03-01165n/an/a10.1111/1759-7714.70023NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNAZhilong Li0Xianzhen Wu1Department of Thoracic Surgery Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University Taiyuan Shanxi ChinaDepartment of Respiratory Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University Taiyuan Shanxi ChinaABSTRACT Background 5‐methylcytosine (m5C) methylation is the crucial posttranscriptional modification of RNA. NSUN4, a methyltransferase for m5C methylation, contributes to lung tumorigenesis. Here, we determined the precise action of NSUN4 on the development of non‐small cell lung cancer (NSCLC). Methods NSUN4 and CDC20 mRNA expression was detected by quantitative PCR. Western blot and immunohistochemistry were used for the analysis of protein expression. Cell growth, apoptosis, invasiveness, migratory ability, and stemness potential were evaluated by colony formation, flow cytometry, transwell, and sphere formation assays. The influence of NSUN4 in CDC20 mRNA was analyzed using RNA immunoprecipitation (RIP) assay and Actinomycin D (Act D) treatment. Subcutaneous xenograft studies were performed to analyze the function in vivo. Results In human NSCLC tumors and cell lines, NSUN4 and CDC20 levels were upregulated. NSUN4 inhibition diminished NSCLC cell growth, stemness, invasiveness, and migratory ability in vitro, while NSUN4 increase had opposite effects. A positive expression association between CDC20 and NSUN4 was observed in NSCLC samples. Mechanistically, NSUN4 enhanced the stability of CDC20 mRNA through m5C modification. CDC20 depletion significantly counteracted NSUN4‐driven cell phenotype alterations in vitro. Additionally, inhibition of NSUN4 impeded the growth of A549 NSCLC subcutaneous xenografts in vivo. Conclusion Our findings identify the pro‐tumorigenic property of the NSUN4/CDC20 cascade in NSCLC. Targeting the novel cascade may be a promising way for combating this deadly disease.https://doi.org/10.1111/1759-7714.70023CDC20m5C methylationmethyltransferaseNSCLCNSUN4 |
| spellingShingle | Zhilong Li Xianzhen Wu NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA Thoracic Cancer CDC20 m5C methylation methyltransferase NSCLC NSUN4 |
| title | NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA |
| title_full | NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA |
| title_fullStr | NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA |
| title_full_unstemmed | NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA |
| title_short | NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA |
| title_sort | nsun4 facilitates the activity of oncogenic protein cdc20 to promote nsclc development by mediating m5c modification of cdc20 mrna |
| topic | CDC20 m5C methylation methyltransferase NSCLC NSUN4 |
| url | https://doi.org/10.1111/1759-7714.70023 |
| work_keys_str_mv | AT zhilongli nsun4facilitatestheactivityofoncogenicproteincdc20topromotensclcdevelopmentbymediatingm5cmodificationofcdc20mrna AT xianzhenwu nsun4facilitatestheactivityofoncogenicproteincdc20topromotensclcdevelopmentbymediatingm5cmodificationofcdc20mrna |