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MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2015 Aug 07; Vol. 463 (4), pp. 954-60. Date of Electronic Publication: 2015 Jun 09. - Publication Year :
- 2015
-
Abstract
- MicroRNAs (miRs) dysregulation is a general feature of colorectal cancer (CRC) and other solid tumors, and is associated cancer progression. In the current study, we demonstrate that microRNA-101 (miR-101) inhibits CRC cells probably through down-regulating sphingosine kinase 1 (SphK1). Our results showed that exogenously expressing miR-101 inhibited CRC cell (HT-29 and HCT-116 lines) growth in vitro. At the molecular level, miR-101 dramatically down-regulated SphK1 mRNA and protein expression, causing pro-apoptotic ceramide production in above CRC cells. On the other hand, inhibition of miR-101 through expressing antagomiR-101 increased SphK1 expression to down-regulate ceramide level in HT-29 cells. miR-101 expression increased the in vitro anti-CRC activity of conventional chemo-agents: paclitaxel and doxorubicin. CRC cells with SphK1-shRNA knockdown showed similar phenotypes as the miR-101-expressed CRC cells, presenting with elevated level of ceramide and high sensitivity to paclitaxel or doxorubicin. In vivo, HCT-116 xenograft growth in severe combined immuno-deficient (SCID) mice was dramatically inhibited by over-expressing miR-101. Further, miR-101 enhanced paclitaxel-induced anti-HCT-116 activity in vivo. Together, these results indicate that miR-101 exerts its anti-CRC activities probably through down-regulating SphK1.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents, Phytogenic pharmacology
Base Sequence
Cell Division physiology
Colorectal Neoplasms pathology
DNA Primers
HT29 Cells
Humans
Mice
Mice, SCID
Paclitaxel pharmacology
Real-Time Polymerase Chain Reaction
Colorectal Neoplasms enzymology
Down-Regulation physiology
MicroRNAs physiology
Phosphotransferases (Alcohol Group Acceptor) metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 463
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 26071354
- Full Text :
- https://doi.org/10.1016/j.bbrc.2015.06.041