[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Yang, Chia-Pei; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
Yang, Wan-Shan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
Wong, Yu-Hui; Brain Research Center, National Yang-Ming University, Taipei, Taiwan
Wang, Kai-Hsuan; Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan
Teng, Yuan-Chi; Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University and Academia Sinica, Taipei, Taiwan ; Department of Life Sciences, Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
Chang, Ming-Hsuan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
Liao, Ko-Hsun; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
Nian, Fang-Shin ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan ; Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan
Chao, Chuan-Chuan; The Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Tsai, Jin-Wu; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
Hwang, Wei-Lun; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan
Lin, Ming-Wei; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
Tzeng, Tsai-Yu; Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan
Wang, Pei-Ning; Brain Research Center, National Yang-Ming University, Taipei, Taiwan ; Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan ; Aging and Health Research Center, National Yang-Ming University, Taipei, Taiwan
Campbell, Mel; UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA
Chen, Liang-Kung; Aging and Health Research Center, National Yang-Ming University, Taipei, Taiwan ; Department of Geriatric Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan ; Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan
Tsai, Ting-Fen; Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan ; Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University and Academia Sinica, Taipei, Taiwan ; Department of Life Sciences, Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan ; Aging and Health Research Center, National Yang-Ming University, Taipei, Taiwan
Chang, Pei-Ching ; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan ; Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan
Kung, Hsing-Jien; Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan ; The Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan ; UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA
This paper is dedicated memorializing Dr. Hsei-Wei Wang, Apr 1969 ~ Sep 2015, who initiated this project in 2014. The work was supported by grants (MOST 105-2633-B-400-001-003 to HJK, PCC, and TFT; MOST 105-2320-B-038-071-MY3, MOST 106-2314-B-038-093 and 107-2320-B-038-055-MY3 to HJK; MOST 105-2320-B-010-007-MY3 to PCC; MOST 107-3011-B-010-001 to TFT, and MOST-108-2321-B-010-013-MY2 to PNW). This work was also financially supported by the “Cancer Progression Research Center, National Yang-Ming University” and “Cancer Center, Taipei Medical University” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan to PCC and HJK, respectively. The authors acknowledge the “High-throughput Genome and Big Data Analysis Core Facility of National Core Facility Program for Biotechnology, Taiwan (MOST 105-2319-B-010-001)” for high-throughput sequencing and the “Cancer Progression Research Center-Genome Editing Core Facility of Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by MOE” for CISD2 CRISPR KO C2C12 cell line. We thank Yi-Lin Chung and Ting-Kuan Chu for their help with the histological analyses of Figure a and Figure S5, respectively. We acknowledge the strong support of the NTU-AS joint laboratory from Dr. Yen Yun, TMU, AS IBC, and NTU IBS.This paper is dedicated memorializing Dr. Hsei‐Wei Wang, Apr 1969 ~ Sep 2015, who initiated this project in 2014. The work was supported by grants (MOST 105‐2633‐B‐400‐001‐003 to HJK, PCC, and TFT; MOST 105‐2320‐B‐038‐071‐MY3, MOST 106‐2314‐B‐038‐093 and 107‐2320‐B‐038‐055‐MY3 to HJK; MOST 105‐2320‐B‐010‐007‐MY3 to PCC; MOST 107‐3011‐B‐010‐001 to TFT, and MOST‐108‐2321‐B‐010‐013‐MY2 to PNW). This work was also financially supported by the “Cancer Progression Research Center, National Yang‐Ming University” and “Cancer Center, Taipei Medical University” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan to PCC and HJK, respectively. The authors acknowledge the “High‐throughput Genome and Big Data Analysis Core Facility of National Core Facility Program for Biotechnology, Taiwan (MOST 105‐2319‐B‐010‐001)” for high‐throughput sequencing and the “Cancer Progression Research Center‐Genome Editing Core Facility of Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by MOE” for CISD2 CRISPR KO C2C12 cell line. We thank Yi‐Lin Chung and Ting‐Kuan Chu for their help with the histological analyses of Figure a and Figure S5 , respectively. We acknowledge the strong support of the NTU‐AS joint laboratory from Dr. Yen Yun, TMU, AS IBC, and NTU IBS.
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