CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability
Abstract Background Pancreatic cancer (PC) is highly aggressive and fatal and has dismal prognostic outcomes, primarily due to its late-stage diagnosis and limited effective treatments. The molecular mechanisms triggering PC progression are largely unclear. This study investigated how CX26 contribut...
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BMC
2025-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06983-5 |
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| author | Cheng He Chuanyu Tang Jie Guo Xiangyi Yin Qing Zhu Chihua Fang |
| author_facet | Cheng He Chuanyu Tang Jie Guo Xiangyi Yin Qing Zhu Chihua Fang |
| author_sort | Cheng He |
| collection | DOAJ |
| description | Abstract Background Pancreatic cancer (PC) is highly aggressive and fatal and has dismal prognostic outcomes, primarily due to its late-stage diagnosis and limited effective treatments. The molecular mechanisms triggering PC progression are largely unclear. This study investigated how CX26 contributes to pancreatic cancer development and its potential as a therapeutic target. Methods CX26 expression in PC and its clinical significance were examined through bioinformatics analysis. The biological functions of CX26 in PC cells were explored via colony formation, CCK-8, and proteomic analysis. To explore the mechanisms by which CX26 regulates c-Myc stability, co-immunoprecipitation, immunofluorescence, and molecular docking were utilized to investigate the interactions among CX26, PSMD2, and c-Myc. Additionally, subcutaneous xenografts in nude mice were applied to assess the impact of CX26 on PC progression in vivo. Results Bioinformatics analysis indicated the upregulation of CX26 in PC tissues. In addition, CX26 expression was closely related to dismal prognostic outcomes. Further study revealed that CX26 promotes PC progression in vitro and in vivo. Proteomic analysis identified c-Myc as the key downstream target of CX26. Mechanistically, CX26 indirectly regulated c-Myc stability via PSMD2 rather than directly interacting with c-Myc. Moreover, CX26 competes with c-Myc to bind to the Armadillo-like helical domain of PSMD2, thereby preventing c-Myc proteasomal degradation. Conclusions This study suggests that CX26 facilitates PC progression by stabilizing c-Myc through competitively inhibiting the binding of PSMD2 to c-Myc. Given the challenges in directly inhibiting c-Myc, this novel regulatory mechanism provides valuable insights into PC biology and reveals that targeting CX26 is a possible way to promote c-Myc degradation and suppress PC growth. |
| format | Article |
| id | doaj-art-0a753a07389644ba977f95eae11a8c0a |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-0a753a07389644ba977f95eae11a8c0a2025-08-24T11:48:07ZengBMCJournal of Translational Medicine1479-58762025-08-0123111410.1186/s12967-025-06983-5CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stabilityCheng He0Chuanyu Tang1Jie Guo2Xiangyi Yin3Qing Zhu4Chihua Fang5Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityAbstract Background Pancreatic cancer (PC) is highly aggressive and fatal and has dismal prognostic outcomes, primarily due to its late-stage diagnosis and limited effective treatments. The molecular mechanisms triggering PC progression are largely unclear. This study investigated how CX26 contributes to pancreatic cancer development and its potential as a therapeutic target. Methods CX26 expression in PC and its clinical significance were examined through bioinformatics analysis. The biological functions of CX26 in PC cells were explored via colony formation, CCK-8, and proteomic analysis. To explore the mechanisms by which CX26 regulates c-Myc stability, co-immunoprecipitation, immunofluorescence, and molecular docking were utilized to investigate the interactions among CX26, PSMD2, and c-Myc. Additionally, subcutaneous xenografts in nude mice were applied to assess the impact of CX26 on PC progression in vivo. Results Bioinformatics analysis indicated the upregulation of CX26 in PC tissues. In addition, CX26 expression was closely related to dismal prognostic outcomes. Further study revealed that CX26 promotes PC progression in vitro and in vivo. Proteomic analysis identified c-Myc as the key downstream target of CX26. Mechanistically, CX26 indirectly regulated c-Myc stability via PSMD2 rather than directly interacting with c-Myc. Moreover, CX26 competes with c-Myc to bind to the Armadillo-like helical domain of PSMD2, thereby preventing c-Myc proteasomal degradation. Conclusions This study suggests that CX26 facilitates PC progression by stabilizing c-Myc through competitively inhibiting the binding of PSMD2 to c-Myc. Given the challenges in directly inhibiting c-Myc, this novel regulatory mechanism provides valuable insights into PC biology and reveals that targeting CX26 is a possible way to promote c-Myc degradation and suppress PC growth.https://doi.org/10.1186/s12967-025-06983-5Pancreatic cancerCX26c-MycPSMD2Proteasomal degradation |
| spellingShingle | Cheng He Chuanyu Tang Jie Guo Xiangyi Yin Qing Zhu Chihua Fang CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability Journal of Translational Medicine Pancreatic cancer CX26 c-Myc PSMD2 Proteasomal degradation |
| title | CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability |
| title_full | CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability |
| title_fullStr | CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability |
| title_full_unstemmed | CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability |
| title_short | CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability |
| title_sort | cx26 promotes pancreatic cancer progression by competitively inhibiting interaction of c myc with psmd2 and enhancing c myc stability |
| topic | Pancreatic cancer CX26 c-Myc PSMD2 Proteasomal degradation |
| url | https://doi.org/10.1186/s12967-025-06983-5 |
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