Universität zu Köln

Yu, Xiaojie ORCID: 0000-0001-9777-8553, Eischeid-Scholz, Hannah, Meder, Lydia, Kondylis, Vangelis, Buettner, Reinhard and Odenthal, Margarete (2022). SQSTM1/p62 promotes miR-198 loading into extracellular vesicles and its autophagy-related secretion. Hum. Cell, 35 (6). S. 1766 - 1785. TOKYO: SPRINGER JAPAN KK. ISSN 1749-0774

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Abstract

MicroRNA dysregulation is a hallmark of hepatocellular carcinoma (HCC), leading to tumor growth and metastasis. Previous screening on patient specimens identified miR-198 as the most downregulated miRNA in HCC. Here, we show that miR-198 compensation leads to self-release into extracellular vesicles (EVs). Importantly, the vesicular secretion is mediated by autophagy-related pathway, initiated by sequestration of p62/miR-198 complexes in autophagosome-associated vesicle fractions. miR-198 is selectively recognized and loaded by p62 into autophagosomal fractions, whereas mutated miR-198 forms neither induce autophagy and nor interact with p62. Gain and loss of function experiments, using a CRIPR/Cas knockout (KO) and transgenic site-specific p62 mutants, identified p62 as an essential repressor of cellular miR-198 abundancy. Notably, EVs, harboring miR-198/p62 protein complexes, can be uptaken by cells in the close vicinity, leading to change of gene expression in recipient cells. In conclusion, miR-198 enhances autophagy; conversely autophagic protein p62 reduces the miR-198 levels by sorting into extracellular space. [GRAPHICS] .

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Yu, Xiaojie UNSPECIFIED orcid.org/0000-0001-9777-8553 UNSPECIFIED Eischeid-Scholz, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Meder, Lydia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kondylis, Vangelis UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-658987
DOI:	10.1007/s13577-022-00765-7
Journal or Publication Title:	Hum. Cell
Volume:	35
Number:	6
Page Range:	S. 1766 - 1785
Date:	2022
Publisher:	SPRINGER JAPAN KK
Place of Publication:	TOKYO
ISSN:	1749-0774
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATOCELLULAR-CARCINOMA; SUPPRESSES TUMORIGENESIS; MICRORNAS; CELLS; GENE; DEGRADATION; DELIVERY; P62 Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/65898