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Biochem Biophys Res Commun. 2015 Aug 7;463(4):954-60. doi: 10.1016/j.bbrc.2015.06.041. Epub 2015 Jun 9.

MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells.

Author information

1
Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China; Department of Radiotherapy and Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, China.
2
Department of Breast Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China.
3
Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
4
Jiangsu University Health Science Center, Jiangsu, China.
5
Department of Radiotherapy and Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, China.
6
Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China. Electronic address: drzhuyaqun@sina.com.
7
Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China. Electronic address: tianyesuzhoua163@163.com.

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.

KEYWORDS:

Ceramide and chemo-sensitization; Colorectal cancer; SphK1; miRNA-101

PMID:
26071354
DOI:
10.1016/j.bbrc.2015.06.041
[Indexed for MEDLINE]

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