Reduced expression of the RNA-binding protein HuD in pancreatic neuroendocrine tumors correlates with low p27Kip1 levels and poor prognosis.

The Journal of Pathology
Chongtae KimWook Kim

Abstract

For the majority of patients diagnosed with pancreatic neuroendocrine tumors (NETs), there is significant malignant potential with a poor prognosis; however, the molecular abnormalities and pathogenesis of pancreatic NETs have not been firmly established. Here, we report that loss of expression of the RNA-binding protein HuD correlates with low p27Kip1 (p27) levels and poor prognosis in pancreatic NETs. HuD expression was frequently lost in many human pancreatic NETs, and these pancreatic NETs showed aggressive clinicopathological phenotypes with low p27 levels, increased tumor size, higher World Health Organization grade and pT stage of the tumor, and the presence of angioinvasion. Furthermore, loss of HuD was an independent, progression-free prognostic factor in multivariate survival analysis. However, the level of HuR, a member of the same Hu protein family as HuD, was not significantly correlated with pancreatic NET size and progression. Mechanistically, HuD enhanced p27 mRNA translation by interacting with both the 5'-untranslated region (UTR) and the 3'-UTR of p27 mRNA, and consequently suppressed cell cycle progression and tumor growth. In addition, HuD competed with miR-30a-3p for binding to the 3'-UTR of p27 mRNA, sugg...Continue Reading

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Citations

Oct 30, 2019·Cell Death and Differentiation·Youlim HongEun Kyung Lee
May 16, 2020·Frontiers in Bioengineering and Biotechnology·Qiuliang YanJinhui Zhu
Aug 24, 2020·Biochemical and Biophysical Research Communications·Sojin AhnEun Kyung Lee
Jun 3, 2021·International Journal of Molecular Sciences·Chisato KinoshitaKoji Aoyama
Sep 18, 2021·Journal of Biomedical Research·Xin LiEugene Yujun Xu

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