Eun Ryeong LEE, Kisang KWON, O Yu KWON, Kyoungmin MOON, Junghae KIM

mir-331 negatively regulates thyroglobulin secretion via ERp29

We investigated the effect of endoplasmic reticulum (ER) protein 29 (ERp29) on thyroglobulin (Tg) secretion and its negativeregulation by microRNAs (miRNAs). ERp29 overexpression promoted Tg secretion from thyrocytes of PCCL3 cells via activation ofER stress sensors, including activation of transcription factor 6 fragmentation, XBP1 mRNA splicing by inositol-requiring enzyme 1,and phosphorylation of eukaryotic initiation factor 2 alpha as downstream actions of RNA-dependent protein kinase-like ER kinase.Thyroid hormone receptor beta is a target gene of mir-331, one of the most abundant miRNAs observed in ERp29-overexpressingcells. mir-331 negatively regulated Tg expression and secretion by ~70% compared with the control. To overcome hypothyroidism, Tgsecretion at the molecular level is required to counteract negative regulation of intracellular mir-331. Our findings may provide insightinto the treatment of diseases caused by poor ER protein secretion, including ER storage diseases.

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