Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis. (Cancer Cell. 2014 Nov 10;26(5):707-21.)

報告日期: 2015/04/10
報告時間: 16:00/16:50
報告學生: 賴輝寰(以英文報告)
講評老師: 黃柏憲
附件下載: 下載[1481-1425858861-1.pdf] 

Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis.

Liu YP, Karg M, Harwig A, Herrera-Carrillo E, Jongejan A, van Kampen A, Berkhout B.

Cancer Cell. 2014 Nov 10; 26(5):707-21

Speaker: Lai, Hui-Huang                       Time: 2015/04/10, 16:00~16:50

Commentator: Professor Huang, Po-Hsien         Location: Room 602

Abstract

MicroRNAs (miRNAs) are endogenous short single strand RNA (~22 nucleotides) that have emerged as important regulators of gene expression. MiRNA genes are transcribed by either RNA polymerase II into long primary transcripts (pri-miRNAs) with folding the short hairpin secondary structure. The pri-miRNA as a substrate is cleaved by the RNase III enzyme Drosha in the nucleus to become precursor miRNA (pre-miRNAs). In the cytoplasm the RNase III enzyme Dicer processes pre-miRNAs to a ~20 bp miRNA duplex, further are separated by helicase into a functional guide strand (mature miRNA) which is complementary to the target. The mature miRNA incorporated into the miRNA induced silencing complex (miRISC) which guides the miRNA targeting the messenger RNAs by complement to its 3’ UTRs to repress translation, destabilized or degraded the mRNAs1. Exosomes are ~40 to 100-nm vesicles secreted from a wide range of mammalian cell types. Cell exosomes consist of lipid bilayer membrane and contain proteins, growth factor, mRNA and miRNAs. Several studies demonstrate that miRNAs contained in exosomes that can deliver elements into target cells2. Dicer and Drosha protein are exist in exosomes and RISC complex also been found presenting in exosomes3. However, functional of miRNA biogenesis factors in cancer-derived exosomes is still unclear. These study demonstrate that cancer-derived exosomes mediate miRNAs in target cells via RISC-complex that promote tumor progression.

References

  1. Krol, J., Loedige, I. & Filipowicz, W. The widespread regulation of microRNA biogenesis, function and decay. Nature reviews. Genetics 11, 597-610 (2010).
  2. Kahlert, C. & Kalluri, R. Exosomes in tumor microenvironment influence cancer progression and metastasis. Journal of molecular medicine 91, 431-437 (2013).
  3. Narayanan, A. et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. The Journal of biological chemistry 288, 20014-20033 (2013).