机构：[a]Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China[b]Department of Radiotherapy and Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, China[c]Department of Breast Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China[d]Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China[e]Jiangsu University Health Science Center, Jiangsu, China
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. (C) 2015 Elsevier Inc. All rights reserved.
基金：
This study is supported by the National Natural Science Foundation
(81472786, 81101801, 81101676, 81372411 and 81172128);
Natural Science Foundation of Jiangsu Province (BK2011374), The
Six Talents Peak Project of Jiangsu Province (WSN-012) and Kunshan
Science and Technology Program (KS1132, KS1341).
第一作者机构：[a]Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China[b]Department of Radiotherapy and Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, No. 1055, San Xiang Road, Suzhou, Jiangsu 215004, China.
推荐引用方式(GB/T 7714)：
Min-Bin Chen,Lan Yang,Pei-Hua Lu,et al.MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2015,463(4):954-60.doi:10.1016/j.bbrc.2015.06.041.
APA：
Min-Bin Chen,Lan Yang,Pei-Hua Lu,Xing-Li Fu,Yan Zhang...&Ye Tian.(2015).MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,463,(4)
MLA：
Min-Bin Chen,et al."MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 463..4(2015):954-60
