RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma
Abstract Objective Regulatory Factor X (RFX) transcription factors have been implicated in different cancers. Ras association domain family (RASSF) has been shown clinical significance in lung cancer. This paper was to investigate the interaction of RFX2 and RASSF1 in lung adenocarcinoma (LUAD). Met...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | Cell Division |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13008-025-00147-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849772417343291392 |
|---|---|
| author | Zhenzhen Kong Ping Zhou Jiahao Xu Ying Zhang Yong Wang |
| author_facet | Zhenzhen Kong Ping Zhou Jiahao Xu Ying Zhang Yong Wang |
| author_sort | Zhenzhen Kong |
| collection | DOAJ |
| description | Abstract Objective Regulatory Factor X (RFX) transcription factors have been implicated in different cancers. Ras association domain family (RASSF) has been shown clinical significance in lung cancer. This paper was to investigate the interaction of RFX2 and RASSF1 in lung adenocarcinoma (LUAD). Methods The transcriptome differences of LUAD patients in GSE32863, GSE43458, and GSE21933 datasets were analyzed. A-549 and NCI-H358 cell lines after overexpression of RFX2 were co-cultured with activated CD8+ T cells, and the release of IFN-γ, GZMB, PRF1 by CD8+ T cells, and PD-L1 in the LUAD cells were detected. Cell viability, invasion, and apoptosis were analyzed by CCK-8, Transwell, and TUNEL assays. Dual-luciferase assay and ChIP were conducted to detect the interaction between RFX2 and RASSF1 promoter. An in vivo tumor model was constructed to monitor tumor growth. YAP protein levels and phosphorylation were measured. A-549 and NCI-H358 cells treated with DMSO or PY-60 after RFX2 overexpression were co-cultured with activated CD8+ T cells. Results RFX2 was notably downregulated in LUAD. RFX2 overexpression increased infiltrating CD8+ T cells within transplanted tumors and inhibited immune escape, proliferation, and invasion of LUAD cells. RFX2 was enriched in the RASSF1 promoter, and RFX2 activated RASSF1 transcription by binding to the RASSF1 promoter. RASSF1 knockdown reversed the ability of RFX2 overexpression to inhibit immune escape. RFX2 depletion downregulated RASSF1, which reduced YAP phosphorylation, thus affecting the Hippo pathway to promote the immune escape. Conclusion RFX2 Loss in LUAD downregulates RASSF1 expression and YAP phosphorylation, thereby promoting immune escape through Hippo signaling. |
| format | Article |
| id | doaj-art-2f7faeb00cad42949a8a2c593d13b4e9 |
| institution | DOAJ |
| issn | 1747-1028 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj-art-2f7faeb00cad42949a8a2c593d13b4e92025-08-20T03:02:19ZengBMCCell Division1747-10282025-03-0120111610.1186/s13008-025-00147-zRFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinomaZhenzhen Kong0Ping Zhou1Jiahao Xu2Ying Zhang3Yong Wang4Department of Laboratory, Wujin Hospital Affiliated With Jiangsu UniversityDepartment of Medical Laboratory, Xuzhou Mining Group General HospitalDepartment of Laboratory, Wujin Hospital Affiliated With Jiangsu UniversityDepartment of Laboratory, Wujin Hospital Affiliated With Jiangsu UniversityDepartment of Laboratory, Wujin Hospital Affiliated With Jiangsu UniversityAbstract Objective Regulatory Factor X (RFX) transcription factors have been implicated in different cancers. Ras association domain family (RASSF) has been shown clinical significance in lung cancer. This paper was to investigate the interaction of RFX2 and RASSF1 in lung adenocarcinoma (LUAD). Methods The transcriptome differences of LUAD patients in GSE32863, GSE43458, and GSE21933 datasets were analyzed. A-549 and NCI-H358 cell lines after overexpression of RFX2 were co-cultured with activated CD8+ T cells, and the release of IFN-γ, GZMB, PRF1 by CD8+ T cells, and PD-L1 in the LUAD cells were detected. Cell viability, invasion, and apoptosis were analyzed by CCK-8, Transwell, and TUNEL assays. Dual-luciferase assay and ChIP were conducted to detect the interaction between RFX2 and RASSF1 promoter. An in vivo tumor model was constructed to monitor tumor growth. YAP protein levels and phosphorylation were measured. A-549 and NCI-H358 cells treated with DMSO or PY-60 after RFX2 overexpression were co-cultured with activated CD8+ T cells. Results RFX2 was notably downregulated in LUAD. RFX2 overexpression increased infiltrating CD8+ T cells within transplanted tumors and inhibited immune escape, proliferation, and invasion of LUAD cells. RFX2 was enriched in the RASSF1 promoter, and RFX2 activated RASSF1 transcription by binding to the RASSF1 promoter. RASSF1 knockdown reversed the ability of RFX2 overexpression to inhibit immune escape. RFX2 depletion downregulated RASSF1, which reduced YAP phosphorylation, thus affecting the Hippo pathway to promote the immune escape. Conclusion RFX2 Loss in LUAD downregulates RASSF1 expression and YAP phosphorylation, thereby promoting immune escape through Hippo signaling.https://doi.org/10.1186/s13008-025-00147-zRFX2Lung adenocarcinomaRASSF1Hippo signaling pathwayImmune escape |
| spellingShingle | Zhenzhen Kong Ping Zhou Jiahao Xu Ying Zhang Yong Wang RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma Cell Division RFX2 Lung adenocarcinoma RASSF1 Hippo signaling pathway Immune escape |
| title | RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma |
| title_full | RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma |
| title_fullStr | RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma |
| title_full_unstemmed | RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma |
| title_short | RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma |
| title_sort | rfx2 downregulates rassf1 expression and yap phosphorylation through hippo signaling to promote immune escape in lung adenocarcinoma |
| topic | RFX2 Lung adenocarcinoma RASSF1 Hippo signaling pathway Immune escape |
| url | https://doi.org/10.1186/s13008-025-00147-z |
| work_keys_str_mv | AT zhenzhenkong rfx2downregulatesrassf1expressionandyapphosphorylationthroughhipposignalingtopromoteimmuneescapeinlungadenocarcinoma AT pingzhou rfx2downregulatesrassf1expressionandyapphosphorylationthroughhipposignalingtopromoteimmuneescapeinlungadenocarcinoma AT jiahaoxu rfx2downregulatesrassf1expressionandyapphosphorylationthroughhipposignalingtopromoteimmuneescapeinlungadenocarcinoma AT yingzhang rfx2downregulatesrassf1expressionandyapphosphorylationthroughhipposignalingtopromoteimmuneescapeinlungadenocarcinoma AT yongwang rfx2downregulatesrassf1expressionandyapphosphorylationthroughhipposignalingtopromoteimmuneescapeinlungadenocarcinoma |