title: MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells.
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.
authors.affiliation: 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.
authors.forename: Min-Bin
authors.initials: MB
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Lu
authors.affiliation: Jiangsu University Health Science Center, Jiangsu, China.
authors.forename: Xing-Li
authors.initials: XL
authors.lastname: Fu
authors.affiliation: Department of Radiotherapy and Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ya-Qun
authors.initials: YQ
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000502:physiology*; D017239:Paclitaxel / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000099157:Sphingosine Kinase
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D035683:MicroRNAs; D017239:Paclitaxel; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase; C534072:MIRN101 microRNA, human
keywords: Ceramide and chemo-sensitization; Colorectal cancer; SphK1; miRNA-101