miR-3156-5p is downregulated in serum of MEN1 patients and regulates expression of MORF4L2

Autor:	Kreepa G Kooblall, Victoria J Stokes, Omair A Shariq, Katherine A English, Mark Stevenson, John Broxholme, Benjamin Wright, Helen E Lockstone, David Buck, Simona Grozinsky-Glasberg, Christopher J Yates, Rajesh V Thakker, Kate E Lines
Rok vydání:	2022
Předmět:	Adult Aged 80 and over Cancer Research Adolescent Endocrinology Diabetes and Metabolism Middle Aged MicroRNAs Young Adult Endocrinology Oncology Child Preschool Mutation Multiple Endocrine Neoplasia Type 1 Quality of Life Humans Child Aged Transcription Factors
Zdroj:	Endocrine-Related Cancer. 29:557-568
ISSN:	1479-6821 1351-0088
Popis:	Multiple endocrine neoplasia type 1 (MEN1), caused by mutations in the MEN1 gene encoding menin, is an autosomal dominant disorder characterised by the combined occurrence of parathyroid, pituitary and pancreatic neuroendocrine tumours (NETs). Development of these tumours is associated with wide variations in their severity, order and ages (from 80 years), requiring life-long screening. To improve tumour surveillance and quality of life, better circulating biomarkers, particularly for pancreatic NETs that are associated with higher mortality, are required. We, therefore, examined the expression of circulating miRNA in the serum of MEN1 patients. Initial profiling analysis followed by qRT-PCR validation studies identified miR-3156-5p to be significantly downregulated (−1.3 to 5.8-fold, P MEN1 knock-down experiments in BON-1 human pancreatic NET cells resulted in reduced MEN1 (49%, P P miR-3156-5p expression (20%, P miR-3156-5p downregulation is a consequence of loss of MEN1 expression. In silico analysis identified mortality factor 4-like 2 (MOR4FL2) as a potential target of miR-3156-5p, and in vitro functional studies in BON-1 cells transfected with either miR-3156-5p mimic or inhibitors showed that the miR-3156-5p mimic significantly reduced MORF4L2 protein expression (46%, P miR-3156-5p inhibitor significantly increased MORF4L2 expression (1.5-fold, P miR-3156-5p regulates MORF4L2 expression. Thus, the inverse relationship between miR-3156-5p and MORF4L2 expression represents a potential serum biomarker that could facilitate the detection of NET occurrence in MEN1 patients.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da6064ac844ac3ef5945d7eafc8f9477 https://doi.org/10.1530/erc-22-0045 Zobrazit plný text záznamu