Abstract
Pancreatic ductal adenocarcinoma (PDAC) is insidious and highly malignant with extremely poor prognosis and drug resistance to current chemotherapies. Therefore, there is a critical need to investigate the molecular mechanism underlying PDAC progression to develop promising diagnostic and therapeutic interventions. In parallel, vacuolar protein sorting (VPS) proteins, involved in the sorting, transportation, and localization of membrane proteins, have gradually attracted the attention of researchers in the development of cancers. Although VPS35 has been reported to promote carcinoma progression, the specific molecular mechanism is still unclear. Here, we determined the impact of VPS35 on the tumorigenesis of PDAC and explored the underlying molecular mechanism. We performed a pan-cancer analysis of 46 VPS genes using RNAseq data from GTEx (control) and TCGA (tumor) and predicted potential functions of VPS35 in PDAC by enrichment analysis. Furthermore, cell cloning experiments, gene knockout, cell cycle analysis, immunohistochemistry, and other molecular and biochemical experiments were used to validate the function of VPS35. Consequently, VPS35 was found overexpressed in multiple cancers and correlated with the poor prognosis of PDAC. Meanwhile, we verified that VPS35 could modulate the cell cycle and promote tumor cell growth in PDAC. Collectively, we provide solid evidence that VPS35 facilitates the cell cycle progression as a critical novel target in PDAC clinical therapy.
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The datasets presented in this study are available from the corresponding author on reasonable request.
Change history
16 May 2024
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s10142-024-01383-2
Notes
Cancer Research UK, (2022). Pancreatic cancer mortality statistics. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/pancreas/mortality [Accessed December 13, 2022].
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Acknowledgements
We appreciated the generosity of Professor Cun Wang in providing the plasmid. We thanked the public databases TCGA, GTEx, and GEO for data collection.
Funding
This study was supported by the National Natural Science Foundation of China (no.82273228 and no. 82173153).
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HL, MM, and HN initiated the concept and reviewed the manuscript. YG, LQ, HP, YL, HW, SH, and SZ performed the experiments. HL analyzed the RNAseq data. SJ, JL, XZ, and XY supervised this study. YG and LQ wrote the draft of the manuscript. All authors contributed to the manuscript revision and approved the submitted version.
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This study was approved by the Research Ethics Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (approval number RA-2021–295).
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Yanzhi Gai and Liheng Qian contributed equally to this work.
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Gai, Y., Qian, L., Jiang, S. et al. RETRACTED ARTICLE: Vacuolar protein sorting 35 (VPS35) acts as a tumor promoter via facilitating cell cycle progression in pancreatic ductal adenocarcinoma. Funct Integr Genomics 23, 90 (2023). https://doi.org/10.1007/s10142-023-01020-4
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DOI: https://doi.org/10.1007/s10142-023-01020-4