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1.
Aging Cell ; 19(5): e13107, 2020 05.
Article in English | MEDLINE | ID: mdl-32233025

ABSTRACT

In mammals, microRNAs can be actively secreted from cells to blood. miR-29b-3p has been shown to play a pivotal role in muscle atrophy, but its role in intercellular communication is largely unknown. Here, we showed that miR-29b-3p was upregulated in normal and premature aging mouse muscle and plasma. miR-29b-3p was also upregulated in the blood of aging individuals, and circulating levels of miR-29b-3p were negatively correlated with relative appendicular skeletal muscle. Consistently, miR-29b-3p was observed in exosomes isolated from long-term differentiated atrophic C2C12 cells. When C2C12-derived miR-29b-3p-containing exosomes were uptaken by neuronal SH-SY5Y cells, increased miR-29b-3p levels in recipient cells were observed. Moreover, miR-29b-3p overexpression led to downregulation of neuronal-related genes and inhibition of neuronal differentiation. Interestingly, we identified HIF1α-AS2 as a novel c-FOS targeting lncRNA that is induced by miR-29b-3p through down-modulation of c-FOS and is required for miR-29b-3p-mediated neuronal differentiation inhibition. Our results suggest that atrophy-associated circulating miR-29b-3p may mediate distal communication between muscle cells and neurons.


Subject(s)
Exosomes/metabolism , MicroRNAs/genetics , Muscle Fibers, Skeletal/metabolism , Muscular Atrophy/metabolism , Neurons/metabolism , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Animals , Cell Differentiation , Cells, Cultured , Cellular Senescence , Humans , Mice
2.
Cancer Lett ; 433: 43-52, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29944905

ABSTRACT

Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an aggressive and metastatic form of PCa. In addition to androgen receptor (AR) signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent reports demonstrate that the downregulation of repressor element-1 silencing transcription factor (REST) protein is a key step in NED of PCa cells. Here, we report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa cells and in CRPC. HOTAIR overexpression is sufficient to induce, whereas knockdown of HOTAIR suppressed NED of PCa cells. Gene ontology (GO) analysis of differentially expressed genes under HOTAIR overexpression and in CRPC versus benign prostatic hyperplasia (BPH) suggests that HOTAIR may participate in PCa progression. Taken together, our results provide the first evidence of lncRNA HOTAIR as a driver for NED of PCa cells.


Subject(s)
Neurosecretory Systems/cytology , Prostatic Neoplasms, Castration-Resistant/genetics , RNA, Long Noncoding/genetics , Repressor Proteins/genetics , Up-Regulation , Cell Differentiation , Cell Line, Tumor , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Male , Prostatic Neoplasms, Castration-Resistant/metabolism , Repressor Proteins/metabolism , Sequence Analysis, RNA
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