Selective activation of miRNAs of the primate-specific chromosome 19 miRNA cluster (C19MC) in cancer and stem cells and possible contribution to regulation of apoptosis

Journal of Biomedical Science

Research

Chiu-Jung Huang¹  Kong Bung Choo²  Soon Keng Cheong³  Phan Nguyen Nhi Nguyen⁴  Shigeki Sugii⁵ 

[1] Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, 43000, Kajang, Selangor, Malaysia;Department of Animal Science & Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan;Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, 43000, Kajang, Selangor, Malaysia;Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, Center for Stem Cell Research, Universiti Tunku Abdul Rahman, Sungai Long campus, Bandar Sungai Long, Cheras, 43000, Kajang, Selangor Darul Ehsan, Malaysia;Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, 43000, Kajang, Selangor, Malaysia;Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, 43000, Kajang, Selangor, Malaysia;Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, 43000, Kajang, Selangor, Malaysia;Postgraduate Program, Universiti Tunku Abdul Rahman, 43000, Kajang, Selangor, Malaysia;Singapore BioImaging Consortium, A*Star, Singapore, Singapore;Duke-NUS Graduate Medical School, Singapore, Singapore;

关键词: C19MC;    Cancer;    Apoptosis;    miRNA expression;    Stem cells;   

DOI  :  10.1186/s12929-017-0326-z

 received in 2016-11-01, accepted in 2017-02-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe human chromosome 19 miRNA cluster (C19MC) of 43 genes is a primate-specific miRNA cluster that may have biological significance in the genetic complexity of the primate. Despite previous reports on individual C19MC miRNA expression in cancer and stem cells, systematic studies on C19MC miRNA expression and biological functions are lacking.ResultsCluster-wide C19MC miRNA expression profiling by microarray analysis showed wholesome C19MC activation in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, in multipotent adipose-derived mesenchymal stem cells (MSCs) and a unipotent human white pre-adipocyte cell line, only selected C19MC miRNAs were expressed. MiRNA copy number analysis also showed selective C19MC expression in cancer cells with expression patterns highly similar to those in MSCs, suggesting similar miRNA regulatory mechanisms in these cells. Selective miRNA expression also suggests complex transcriptional mechanism(s) regulating C19MC expression under specific cellular and pathological conditions. Bioinformatics analysis showed that sixteen of the C19MC miRNAs share the same “AAGUGC” seed sequence with members of the miR-302/-372 family, which are known cellular reprogramming factors. In particular, C19MC-AAGUGC-miRNAs with the nucleotides 2-7 canonical seed position as in miR-302/-372 miRNAs, may play similar roles as miR-302/-372 in induced pluripotency. A biased 3p-arm selection of the C19MC-AAGUGC-miRNAs was observed indicating that targets of the 3p species of these miRNAs may be biologically significant in regulating stemness. Furthermore, bioinformatics analysis of the putative targets of the C19MC-AAGUGC-miRNAs predicted significant involvement of signaling pathways in reprogramming, many of which contribute to promoting apoptosis by indirect activation of the pro-apoptotic proteins BAK/BAX via suppression of genes of the cell survival pathways, or by enhancing caspase-8 activation through targeting inhibitors of TRAIL-inducing apoptosis.ConclusionsThis work demonstrated selective C19MC expression in MSCs and cancer cells, and, through miRNA profiling and bioinformatics analysis, predicted C19MC modulation of apoptosis in induced pluripotency and tumorigenesis.

【 授权许可】

CC BY   
© The Author(s). 2017