SQSTM1/p62 is a prognostic molecular marker and potential therapeutic target for pancreatic neuroendocrine tumours.
Endocrine
; 85(1): 407-416, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38386167
ABSTRACT
BACKGROUND:
There have been few studies on the role of autophagy in pancreatic neuroendocrine tumours (PNETs). SQSTM1/p62 (also called Sequestosome 1) is a potential autophagy regulator, and its biological roles and clinical significance in PNETs remain poorly understood.PURPOSE:
The purpose of this study was to evaluate the clinical significance of SQSTM1/p62 in human PNET specimens and to evaluate its potential value as a therapeutic target by studying its biological function in PNET cell lines.METHODS:
SQSTM1/p62 protein expression was assessed in 106 PNET patient specimens by immunohistochemistry, and the relationship between SQSTM1/p62 protein expression and the clinicopathological features of PNETs in patients was analysed. The proliferation, invasion and apoptosis of SQSTM1/p62-knockdown QGP-1 and INS-1 cells were assessed by the MTT assay, a Transwell assay and flow cytometry. Cell autophagy was assessed by western blotting and mCherry-GFP-LC3B.RESULTS:
The protein expression of SQSTM1/p62 in PNET patient specimens was significantly correlated with tumour recurrence (p = 0.005) and worse prognosis (log rank p = 0.020). Downregulation of the SQSTM1/p62 gene inhibited tumour cell proliferation and migration and induced PNET cell death. Downregulation of SQSTM1/p62 activated autophagy in PNET cell lines but blocked autophagic flow. Knockdown of the SQSTM1/p62 gene inhibited mTOR phosphorylation.CONCLUSION:
The SQSTM1/P62 protein could be an independent prognostic marker for PNET patients. Downregulating SQSTM1/P62 can inhibit PNET progression, inhibit mTOR phosphorylation and block autophagic flow.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
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Autophagy
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Neuroendocrine Tumors
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Cell Proliferation
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Sequestosome-1 Protein
Limits:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Endocrine
Journal subject:
ENDOCRINOLOGIA
Year:
2024
Type:
Article