N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer
Abstract Background Extracellular vesicles (EVs) produced in the tumor microenvironment in response to chemotherapy promote chemotherapy-resistant phenotypes. However, the role of EVs proteins induced by gastric cancer (GC) cell chemotherapy in regulating chemotherapy resistance remains unclear. Met...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-025-06340-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850039547860090880 |
|---|---|
| author | Yuhan Liao Xinhua Chen Hao Xu Yunfei Zhi Xinghua Zhuo Jiang Yu Liang Zhao |
| author_facet | Yuhan Liao Xinhua Chen Hao Xu Yunfei Zhi Xinghua Zhuo Jiang Yu Liang Zhao |
| author_sort | Yuhan Liao |
| collection | DOAJ |
| description | Abstract Background Extracellular vesicles (EVs) produced in the tumor microenvironment in response to chemotherapy promote chemotherapy-resistant phenotypes. However, the role of EVs proteins induced by gastric cancer (GC) cell chemotherapy in regulating chemotherapy resistance remains unclear. Methods Immunohistochemistry was used to verify the relationship between brain-specific angiogenesis inhibitor 1-associated protein-2-like protein 2 (BAIAP2L2) expression and chemotherapy resistance in advanced GC. The relationship between BAIAP2L2 and chemotherapy resistance was verified using a subcutaneous tumor model in nude mice. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were performed to detect purified EVs. Tandem mass tag (TMT) analysis was used to detect differential labels. The interaction between YTH domain-containing family protein1 (YTHDF1) and BAIAP2L2 in GC cells was confirmed by RIP-qPCR analysis using a YTHDF1-specific antibody. Results We found that BAIAP2L2 was associated with chemotherapy resistance to GC in clinical samples and was increased in chemotherapy-resistant GC cells. Mechanistically, BAIAP2L2 promotes the transfer of chemotherapy resistance from resistant GC cells to sensitive cells through EVs proteins, such as ANXA4. Furthermore, ANXA4 promoted platinum-based chemical resistance in GC by mediating autophagy. Interestingly, YTHDF1 facilitates the translation of BAIAP2L2 and ANXA4 through m6A modifications. Conclusions Our findings reveal the key role of BAIAP2L2 as a potential prognostic marker and therapeutic target for chemotherapy resistance in GC. |
| format | Article |
| id | doaj-art-162dd0ea5804499992f20187d2cca80b |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-162dd0ea5804499992f20187d2cca80b2025-08-20T02:56:17ZengBMCJournal of Translational Medicine1479-58762025-03-0123111610.1186/s12967-025-06340-6N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancerYuhan Liao0Xinhua Chen1Hao Xu2Yunfei Zhi3Xinghua Zhuo4Jiang Yu5Liang Zhao6Department of Pathology, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Pathology, Nanfang Hospital, Southern Medical UniversityDepartment of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College HospitalDepartment of Pathology, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Pathology, Nanfang Hospital, Southern Medical UniversityAbstract Background Extracellular vesicles (EVs) produced in the tumor microenvironment in response to chemotherapy promote chemotherapy-resistant phenotypes. However, the role of EVs proteins induced by gastric cancer (GC) cell chemotherapy in regulating chemotherapy resistance remains unclear. Methods Immunohistochemistry was used to verify the relationship between brain-specific angiogenesis inhibitor 1-associated protein-2-like protein 2 (BAIAP2L2) expression and chemotherapy resistance in advanced GC. The relationship between BAIAP2L2 and chemotherapy resistance was verified using a subcutaneous tumor model in nude mice. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were performed to detect purified EVs. Tandem mass tag (TMT) analysis was used to detect differential labels. The interaction between YTH domain-containing family protein1 (YTHDF1) and BAIAP2L2 in GC cells was confirmed by RIP-qPCR analysis using a YTHDF1-specific antibody. Results We found that BAIAP2L2 was associated with chemotherapy resistance to GC in clinical samples and was increased in chemotherapy-resistant GC cells. Mechanistically, BAIAP2L2 promotes the transfer of chemotherapy resistance from resistant GC cells to sensitive cells through EVs proteins, such as ANXA4. Furthermore, ANXA4 promoted platinum-based chemical resistance in GC by mediating autophagy. Interestingly, YTHDF1 facilitates the translation of BAIAP2L2 and ANXA4 through m6A modifications. Conclusions Our findings reveal the key role of BAIAP2L2 as a potential prognostic marker and therapeutic target for chemotherapy resistance in GC.https://doi.org/10.1186/s12967-025-06340-6Gastric cancerBAIAP2L2M6AYTHDF1Extracellular vesiclesChemoresistance |
| spellingShingle | Yuhan Liao Xinhua Chen Hao Xu Yunfei Zhi Xinghua Zhuo Jiang Yu Liang Zhao N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer Journal of Translational Medicine Gastric cancer BAIAP2L2 M6A YTHDF1 Extracellular vesicles Chemoresistance |
| title | N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer |
| title_full | N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer |
| title_fullStr | N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer |
| title_full_unstemmed | N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer |
| title_short | N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer |
| title_sort | n6 methyladenosine rna modified baiap2l2 facilitates extracellular vesicles mediated chemoresistance transmission in gastric cancer |
| topic | Gastric cancer BAIAP2L2 M6A YTHDF1 Extracellular vesicles Chemoresistance |
| url | https://doi.org/10.1186/s12967-025-06340-6 |
| work_keys_str_mv | AT yuhanliao n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer AT xinhuachen n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer AT haoxu n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer AT yunfeizhi n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer AT xinghuazhuo n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer AT jiangyu n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer AT liangzhao n6methyladenosinernamodifiedbaiap2l2facilitatesextracellularvesiclesmediatedchemoresistancetransmissioningastriccancer |