4.6 Article

Hyperglycemia induces gastric carcinoma proliferation and migration via the Pin1/BRD4 pathway

Journal

CELL DEATH DISCOVERY
Volume 8, Issue 1, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41420-022-01030-4

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Funding

  1. National Natural Science Foundation of China [81970370]
  2. Fujian Provincial Health Technology Project [2019-CX-28, 2020QNA056]
  3. Foreign Cooperation Project of Science and Technology, Fujian Province [2021I0013]
  4. Innovation of Science and Technology, Fujian Province [2018Y9113]

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This study found that diabetes is a potential risk factor for gastric cancer. The Pin1/BRD4 axis plays an important role in hyperglycemia-induced proliferation and migration of gastric cancer cells. Inhibition of Pin1 and BRD4 can significantly suppress high-glucose-induced proliferation and migration of gastric cancer cells, leading to improved prognosis for patients.
Diabetes is a potential risk factor for gastric cancer (GC). Pin1, a peptidyl-prolyl cis/trans isomerase, promotes GC cell proliferation and migration. The role and underlying mechanism of the Pin1/BRD4 axis in hyperglycemia-induced proliferation and migration of GC cells were analyzed in vivo and in vitro. Proliferation and migration of GC cells were measured; Pin1 and BRD4 expression of the cell cycle were determined. Pin1 and BRD4 were downregulated by transfecting Pin1 shRNA lentivirus into GC cells and JQ1-intervention GC cells. Tumor formation and lung metastasis were assessed in vivo. Inhibition of Pin1 and BRD4 significantly suppressed high-glucose (HG)-induced GC cell proliferation and migration. HG enhanced G1/S cell-cycle transition, associated with increased Pin1 and BRD4 expression. Silencing Pin1 significantly downregulated the expression of BRD4 and NAP1L1 and upregulated that of P21 in GC cells. In vivo studies indicated that hyperglycemia promotes tumor growth and lung metastasis by inducing Pin1 and BRD4 expression. Thus, Pin1/BRD4 plays an important role in hyperglycemia-promoted tumor growth. The significance of these findings toward improved prognosis of diabetic patients with GC cannot be underestimated.

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