PKHD1L1 blocks the malignant behavior of lung adenocarcinoma cells and restricts tumor growth by regulating CBX7
KEWEI CHENG1, LEI SHI1, CAIWEN SHI1, SHUANSHUAN XIE2, CHANGHUI WANG2,*
1 Department of Pulmonary and Critical Care Medicine, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213004, China
2 Department of Pulmonary and Critical Care Medicine, Shanghai Tenth Clinical Medical College of Nanjing Medical University, Shanghai, 200072, China
* Corresponding Author: CHANGHUI WANG. Email: 
BIOCELL https://doi.org/10.32604/biocell.2024.049626
Received 12 January 2024; Accepted 15 May 2024; Published online 25 June 2024
Abstract
Objective: To explore the role of polycystic kidney and hepatic disease 1-like 1 (PKHD1L1) in lung adenocarcinoma (LUAD).
Methods: Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7 (CBX7) in LUAD. The Cell Counting Kit-8, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling, Transwell, and wound-healing assays were carried out to assess the proliferative, apoptotic, invasive, and migrative capacities of the cells. Furthermore, the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay. A LUAD mice model was constructed by subcutaneous injection of A549 cells. Finally, immunohistochemical staining was performed to evaluate CBX7 and Ki67 expression.
Results: PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with LUAD. PKHD1L1 upregulation repressed the proliferative, invasive, and migrative capabilities of A549 cells and exacerbated the apoptotic rate. Additionally, PKHD1L1 may bind to CBX7 and positively modulate CBX7 expression. CBX7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 cells. Furthermore, the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 cells. PKHD1L1 restricted tumor growth in LUAD xenograft mice; this was partly abolished by CBX7 knockdown.
Conclusion: PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling.
Keywords
Lung adenocarcinoma; Polycystic kidney and hepatic disease 1-like 1; CBX7; Hippo signaling
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