LINC ROR from Hepatocarcinoma Cell-derived Exosomes Modulates Inflammation in Human Macrophages

LI Xue, LI Nan

Abstract

To explore the regulatory function of long intergenic non-coding RNA LINC ROR that contained within hepatocarcinoma cells-derived exosomes. MethodsThe physiological appearance of exosomes isolated from PLC/PRF/5 cells was examined by using differential ultracentrifugation and the images were captured by transmission electron microscopy. The internalization of exosomes by THP-1 cells was examined via laser-scanning confocal microscopy. The expression of LINC ROR was analyzed through qRT-PCR. The expression of interleukin (IL)-1β was examined by ELISA. ResultsExosomes were found spherical and the diameters mainly distribute around 100 nm. LINC ROR can be transferred by tumor derived exosomes to macrophages. Exosomes isolated from PLC/PRF/5 cells significantly expressed higher levels of LINC ROR. Suppression of LINC ROR by siRNA significantly increased the release of pro-inflammatory cytokine (IL-1β) in THP-1 cell upon LPS stimulation. ConclusionLINC ROR from hepatocarcinoma cell-derived exosomes plays an important role in regulating the inflammation of macrophages.

 

Keywords: ExosomesLong intergenic non-coding RNA, LINC ROR, Hepatocarcinoma, Macrophages 

 

Full Text:

PDF


References


SEO HH. LEE SY, LEE CY, et al. Exogenous miRNA- 146a enhances the therapeutic efficacy of human mesenchymal stem cells by increasing vascular endothelial growth factor secretion in the ischemia/reperfusion-injured heart. J Vase Res,2017,54(2): 100-108.

QU B. GONG K, YANG HS, et al. MiR-449 overexpression inhibits osteogenic differentiation of bone marrow mesenchymal stem cells via suppressing Sirtl/Fra-1 pathway in high glucose and free fatty acids microenvironment. Biochem Biophys Res Commun,2018,496 (1):120-126.

LIU L, CHIU PW, LAM PK, et al. Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model. Br J Surg,2015, 102 (2):el58-el68[2018-06-10]. https;//doi. org/10. 1002/bjs. 9724.

KVERNENG HD. ANGENETE E, LYDRUP ML, et al. Nonsteroidal anti-inflammatory drugs and the risk of anastomotic leakage after anterior resection for rectal cancer. Eur J Surg Oncol,2017,43< 10): 1908-1914.

HE R, YIN H, YUAN B, et al. IL-33 improves wound healing through enhanced Mб macrophage polarization in diabetic mice. Mol Immunol, 2017, 90; 42-49 [2018-06-10]. https://doi. org/10. 1016/j. molimm. 2017. 06. 249.

TKACH M. THERY С. Communication by extracellular vesicles; where we are and where we need to go. Cell,2016, 164(6):1226-1232.

HEWARDJA, LINDSAY MA. Long non-coding RNAs in the regulation of the immune response. Trends Immunol, 2014,35(9):408-419.

YU DD, WU Y, SHEN HY, et al. Exosomes in development, metastasis and drug resistance of breast cancer. Cancer Sci,2015.106(8): 959-964.

QUINN JJ, CHANG HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet, 2016б 17(1);47-62.

LU Z, CARTER AC, CHANG HY. Mechanistic insights in X-chromosome inactivation. Philos Trans R Soc Lond В Biol Sci,2017,372( 1733): pii; 20160356[2018-03-08]. https:// doi. org/10. 1098/rstb. 2016. 0356.

LOEWER S, CABILI MN, GUTTMAN M, et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet, 2010, 42 (12):1113-1117.

PAN Y, LI C, CHEN J, et al. The emerging roles of long noncoding RNA ROR ( lincRNA-ROR ) and its possible mechanisms in human cancers. Cell Physiol Biochem, 2016, 40(1/2):219-229.

FAISS, LOGOZZI M, LUGINI L, et al. Exosomes: the ideal nanovectors for biodelivery. Biol Chem,2013,394( 1); 1- 15.

TAYLOR DD. Isolation and molecular characterization of extracellular vesicles. Methods. 2015» 87: 1-2^2018-03-08]. https://doi. org/10. 1016/j. ymeth. 2015. 08. 006.

TAKAHASHI K, YAN IK. HAGA H, et al. Modulation of hypoxia-signaling pathways by extracellular lincRoR. J Cell Sci,2014,127(Pt 7);1585-1594.

KOGURET, YAN IK. LIN WL, et al. Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: a mechanism of intercellular signaling in human hepatocellular cancer. Genes Cancer.2013 .4(7/8): 261-272.

TAKAHASHI K. YAN IK. KXiURE T. et al. Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Bio, 2014, 4; 458-467 [2018-03-08]. http://dx. doi. org/10. 1016/j. fob. 2014. 04. 007.

CHANMEET. ONTONG P. KONNO K, et al. Tumor- associated macrophages as major players in the tumor microenvironment. Cancers (Basel) .2014.6(3): 1670-1690.

САРЕСЕD. FISCHIETTI M, VERZELLA D. et al. The inflammatory microenvironment in hepatocellular carcinoma;a pivotal role for tumor-associated macrophages. Biomed Res Int. 2013. 2013: 187204 [2018-03-08]. http://dx. doi. org/ 10. 1155/2013/187204.

SIMS JE, SMITH DE. The IL-1 family: regulators of immunity. Nat Rev Immunol,2010,10(2) ;89-102.


Refbacks

  • There are currently no refbacks.