2. Academic Validation
  3. PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway

PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway

  • Cell Death Dis. 2023 Aug 25;14(8):558. doi: 10.1038/s41419-023-06069-4.
Ming Cheng # 1,  Hongyi Cao # 1 2,  Peifeng Yao 3,  Jingqian Guan 1,  Peihong Wu 1,  Hairu Ji 4,  Siyu Jiang 1,  Yinan Yuan 1,  Lin Fu 5 6,  Qianqian Zheng 7,  Qingchang Li 8 9
Affiliations

Affiliations

  • 1 Department of Pathology, College of Basic Medical Sciences, China Medical University, 110000, Shenyang, Liaoning Province, People's Republic of China.
  • 2 Department of Pathology, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, 110000, Shenyang, Liaoning Province, People's Republic of China.
  • 3 Department of Hand Surgery, Central Hospital affiliated to Shenyang Medical College, 110000, Shenyang, Liaoning Province, People's Republic of China.
  • 4 Department of Pathology, Chengde Medical University, 067000, Chengde, Hebei Province, People's Republic of China.
  • 5 Department of Pathology, College of Basic Medical Sciences, China Medical University, 110000, Shenyang, Liaoning Province, People's Republic of China. fulin1217@163.com.
  • 6 Department of Pathology, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, 110000, Shenyang, Liaoning Province, People's Republic of China. fulin1217@163.com.
  • 7 Department of Pathophysiology, College of Basic Medical Sciences, China Medical University, 110000, Shenyang, Liaoning Province, People's Republic of China. qqzheng@cmu.edu.cn.
  • 8 Department of Pathology, College of Basic Medical Sciences, China Medical University, 110000, Shenyang, Liaoning Province, People's Republic of China. qcli@cmu.edu.cn.
  • 9 Department of Pathology, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, 110000, Shenyang, Liaoning Province, People's Republic of China. qcli@cmu.edu.cn.
  • # Contributed equally.
PMID: 37626047 DOI: 10.1038/s41419-023-06069-4
Abstract

At present, non-small cell lung Cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung Cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.

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