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CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma

Bioengineered. 2022 May;13(5):13089-13107. doi: 10.1080/21655979.2022.2078940.

Abstract

Pancreatic adenocarcinoma (PAAD) is a common digestive tract malignant tumor with an extremely poor prognosis. The survival and prognosis may significantly improve if it is diagnosed early. Therefore, identifying biomarkers for early diagnosis is still considered a great clinical challenge in PAAD. Cell Division Cycle 25C (CDC25C), a cardinal cell cycle regulatory protein, directly mediates the G2/M phase and is intimately implicated in tumor development. In the current study, we aim to explore the possible functions of CDC25C and determine the potential role of CDC25C in the early diagnosis and prognosis of PAAD. Expression analysis indicated that CDC25C was overexpressed in PAAD . In addition, survival analysis revealed a strong correlation between the enhanced expression of CDC25C and poor survival in PAAD. Furthermore, pathway analysis showed that CDC25C is related to TP53 signaling pathways, glutathione metabolism, and glycolysis. Mechanically, our in vitro experiments verified that CDC25C was capable of promoting cell viability and proliferation. CDC25C inhibition increases the accumulation of ROS, inhibits mitochondrial respiration, suppresses glycolysis metabolism and reduces GSH levels. To summarize, CDC25C may be involved in energy metabolism by maintaining mitochondrial homeostasis. Our results suggested that CDC25C is a potential biological marker and promising therapeutic target of PAAD.

Keywords: CDC25C; GEO; TCGA; bioinformatic analysis; pancreatic adenocarcinoma.

MeSH terms

  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Homeostasis
  • Humans
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • cdc25 Phosphatases* / genetics
  • cdc25 Phosphatases* / metabolism

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • CDC25C protein, human
  • cdc25 Phosphatases

Grants and funding

This research was supported by Zhejiang Provincial Natural Science Foundation of China [Grant Nos. LGF21H010008, LGF20H080005, LGF22H160038, LGF22H160027]; major projects of Hangzhou health science and technology [Z20220024].