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World J Clin Oncol. Sep 24, 2026; 17(9): 122832
Published online Sep 24, 2026. doi: 10.5306/wjco.122832
Correlations of the expression of AKAP95, Cx43, CPSF5/6, SCFFBXL2 and SCFFBXO31 in lung cancer tissues
Zi-Feng Deng, Lei Zhao, Ye Yuan, Li-Kun Li, Mu-Ya Ge, Liang-Ding Dou, Jin-Wen Zhang, Dai Wang, Dong-Bei Guo, Ran An, Yong-Xing Zhang, Bo Song
Zi-Feng Deng, School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong 999077, China
Zi-Feng Deng, Lei Zhao, Liang-Ding Dou, Jin-Wen Zhang, Dai Wang, Dong-Bei Guo, Ran An, Yong-Xing Zhang, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian Province, China
Lei Zhao, Ye Yuan, Li-Kun Li, Mu-Ya Ge, Bo Song, Air Force Hospital of Eastern Theater, Nanjing University of Chinese Medicine, Nanjing 230032, Jiangsu Province, China
Co-first authors: Zi-Feng Deng and Lei Zhao.
Author contributions: Song B designed the research study; Deng ZF and Zhao L performed the research; Dou LD, Zhang JW and Yuan Y analyzed the data; Li LK and Ge MY contributed of pathological tissues; Wang D, Guo DB, An R and Zhang YX gave administrative support; Song B and Zhao L reviewed the manuscript; all authors have read and approved the final manuscript. Deng ZF and Zhao L jointly performed the research; Deng ZF wrote the manuscript, while Zhao L reviewed the manuscript; made equal contributions to the project; following a comprehensive deliberation involving all co-first authors, it has been mutually agreed that Deng ZF and Zhao L be designated as co-first authors.
AI contribution statement: We use GPT-5.6 Sol to polish the language of a small portion of the manuscripts. At the same time, we also entrust it to MedSci to ensure the language meets the standards. No AI tools were used to generate research data, analyze data, or draw conclusions. The author bears full responsibility for this.
Supported by National Natural Science Foundation of China, No. 82272349.
Institutional review board statement: This study was initially approved in 2007 and all participants were informed consent to collect tumor tissue and participate in subsequent studies between 2007-2009 by Shengjing Hospital of China Medical University. Due to multiple uses of the same batch of samples, Ethics Committee of Xiamen University School of Public Health re- examined and approved the study (No. SPHIRB-202001). We declare that our study adhered to the Declaration of Helsinki and we respect dignity, privacy, and rights of all participants.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: All original slices are kept by our laboratory. Please contact
z63y94x@xmu.edu.cn for relevant data.
Corresponding author: Bo Song, PhD, Chief Physician, Professor, Air Force Hospital of Eastern Theater, Nanjing University of Chinese Medicine, No. 1 Changfu Road, Nanjing 230032, Jiangsu Province, China.
23822520@qq.com
Received: May 6, 2026
Revised: August 5, 2026
Accepted: September 15, 2026
Published online: September 24, 2026
Processing time: 146 Days and 17.3 Hours
BACKGROUND
Previous studies suggest that AKAP95 and Cx43 regulate D- and E-type cyclins, but the pathways underlying cyclin degradation remain unclear. The E3 ligases SCFFBXO31 and SCFFBXL2 mediate the degradation of cyclin D1 and cyclin D2/3, respectively, whereas CPSF5 and CPSF6 regulate post-transcriptional gene expression.
AIM
To investigate the relationships among AKAP95, Cx43, SCFFBXO31, SCFFBXL2, CPSF5, and CPSF6 in lung cancer.
METHODS
Protein expression was evaluated by immunohistochemistry in 40 lung cancer tissue samples, and correlations among the six proteins were analyzed. RNA sequencing was used to assess transcript levels in AKAP95-overexpressing A549 cells. Western blotting and densitometric analysis were performed to examine SCFFBXO31 and SCFFBXL2 expression in A549 cells with AKAP95 or Cx43 overexpression or knockdown.
RESULTS
In lung cancer tissues, AKAP95 expression was negatively correlated with SCFFBXO31 and positively correlated with CPSF5, whereas Cx43 expression was positively correlated with SCFFBXO31. No significant correlations were observed between AKAP95 and SCFFBXL2 or CPSF6, or between Cx43 and SCFFBXL2, CPSF5, or CPSF6. In AKAP95-overexpressing A549 cells, the mRNA levels of Cx43, SCFFBXL2, and SCFFBXO31 increased, whereas those of CPSF5 and CPSF6 decreased. At the protein level, SCFFBXL2 was reduced in AKAP95-overexpressing cells, while SCFFBXO31 was reduced by AKAP95 overexpression or Cx43 knockdown and increased by Cx43 overexpression or AKAP95 knockdown.
CONCLUSION
Clinical tissue and cellular findings support roles for AKAP95 and Cx43 in regulating cyclin D expression through SCFFBXO31 and SCFFBXL2.
Core Tip: This study links mechanistic findings to clinical evidence in lung cancer. Immunohistochemical analysis of 40 tumor specimens showed that AKAP95 was negatively correlated with the SCFFBXO31, whereas Cx43 was positively correlated with SCFFBXO31. Complementary cell experiments supported opposing effects of AKAP95 and Cx43 on SCFFBXO31 expression. Together, these findings provide clinical support for a proposed pathway through which the AKAP95-Cx43 axis regulates cyclin D1 degradation and cell-cycle progression.
