The origin of exosomal miR-1246 in human cancer cells

RNA Biology
Yi-Fan XuWei-Qun Ding

Abstract

miR-1246 is considered an oncomiR in various cancer types. However, the origin and biogenesis of miR-1246 remain controversial which often leads to misinterpretation of its detection and biological function, and inevitably masking its mechanisms of action. Using next generation small RNA sequencing, CRISPR-Cas9 knockout, siRNA knockdown and the poly-A tailing SYBR qRT-PCR, we examined the biogenesis of exosomal miR-1246 in human cancer cell model systems. We found that miR-1246 is highly enriched in exosomes derived from human cancer cells and that it originates from RNU2-1, a small nuclear RNA and essential component of the U2 complex of the spliceosome. Knockdown of Drosha and Dicer did not reduce exosomal miR-1246 levels, indicating that exosomal miR-1246 is generated in a Drosha- and Dicer-independent manner. Direct digestion of cellular lysate by RNase A and knockdown of the RNU2-1 binding protein SmB/B' demonstrated that exosomal miR-1246 is a RNU2-1 degradation product. Furthermore, the GCAG motif present in the RUN2-1 transcript was shown to mediate miR-1246 enrichment in cancer exosomes. We conclude that exosome miR-1246 is derived from RNU2-1 degradation through a non-canonical microRNA biogenesis process. These findi...Continue Reading

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Citations

Sep 26, 2019·Journal of Extracellular Vesicles·Martin AuberEva-Maria Krämer-Albers
Sep 12, 2019·International Journal of Clinical Oncology·Yuntao ShiZheng Liu
Jul 28, 2020·International Journal of Molecular Sciences·Aneta ZebrowskaMonika Pietrowska
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Anna E BarryHien Dang
Aug 28, 2020·International Journal of Molecular Sciences·Haoyao SunWei-Qun Ding
Jul 1, 2015·Genes & Cancer·Kambiz AfrasiabiAngela Fleischman
Aug 21, 2020·Cell Communication and Signaling : CCS·Yi-Fan XuWei-Qun Ding
May 21, 2020·International Journal of Molecular Sciences·Dorothea R MorrisJiyang Cai
Jun 8, 2021·Biochemistry and Biophysics Reports·Junfang TuMei He
Jun 25, 2021·Frontiers in Genetics·Shuying ChenYuan Lv
Oct 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Heather E UptonKathleen Collins

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Methods Mentioned

BETA
flow
fluorescence microscopy
PCR
gene knockout
electrophoresis
transfection
X-ray

Software Mentioned

GraphPad Prism
Ensembl
Geospiza
TxetWrangler BONES
Genesifter
GraphPad
Photoshop

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