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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.

Titel:	SQSTM1/p62 is a prognostic molecular marker and potential therapeutic target for pancreatic neuroendocrine tumours.
Autor/in / Beteiligte Person:	Song, YL ; Weng, JH ; Zhao, DC ; Zhang, JL ; Chen, YJ ; Xu, BH
Zeitschrift:	Endocrine, 2024-02-22
Veröffentlichung:	Ahead of Print, 2024
Medientyp:	academicJournal
ISSN:	1559-0100 (electronic)
DOI:	10.1007/s12020-023-03546-w
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(PMID: 10.3390/cancers13246327349449468699234) Grant Information: KJ2018CX008-23 and KJ2019CX014-20 Beijing Tongzhou Science and Technology Planning Project Contributed Indexing: Keywords: Autophagy; Pancreatic neuroendocrine tumours; Prognosis; SQSTM1/p62; mTOR phosphorylation Entry Date(s): Date Created: 20240222 Latest Revision: 20240222 Update Code: 20240222

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SQSTM1/p62 is a prognostic molecular marker and potential therapeutic target for pancreatic neuroendocrine tumours.