Friday, Mar.29, 2024
miRNA:

hsa-miR-100

Disease:

nasopharyngeal carcinoma (NPC)

Relationship type:

Causal

Detection method for miRNA expression:

northern blot, qRT-PCR etc

Expression pattern of miRNA:

down-regulated

Validated targets of miRNA from the reference:

Plk1

Validated targets of miRNA from TarBase:

unknown : More...

Predicted targets: MIRANDA, TARGETSCAN, PICTAR-VERT

 

Description:

Hence, a detailed evaluation was undertaken of Plk1 expression in human nasopharyngeal carcinoma (NPC), the cellular effects of targeting Plk1 using siRNA in combination with ionizing radiation (RT), and potential upstream microRNAs (miRs) that might regulate Plk1 expression. Using immunohistochemistry, Plk1 was observed to be over-expressed in 28 of 40 (70%) primary NPC biopsies, which in turn, was associated with a higher likelihood of recurrence (p=0.018). SiPlk1 significantly inhibited Plk1 mRNA and protein expression, and decreased Cdc25c levels in NPC cell lines. This depletion resulted in cytotoxicity of C666-1 cells, enhanced by the addition of RT, mediated by G2/M arrest, increased DNA double-strand breaks, apoptosis, and caspase activation. Immunofluorescence demonstrated that the G2/M arrest was associated with aberrant spindle formation, leading to mitotic arrest. In vivo, transfection of C666-1 cells and systemic delivery of siPlk1 decreased tumour growth. MicroRNA-100 (miR-100) was predicted to target Plk1 mRNA, which was indeed under-expressed in C666-1 cells; inversely correlating with Plk1 expression. Using luciferase constructs containing the 3'-UTR of Plk1 sequence, we document that miR-100 can directly target Plk1. Hence, our data demonstrate for the first time, that under-expressed miR-100 leads to Plk1 over-expression, which in turn, contributes to NPC progression. Targeting Plk1 will cause mitotic catastrophe, with significant cytotoxicity both in vitro and in vivo, underscoring the important therapeutic opportunity of Plk1 in NPC.

 

 

Reference:

Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer | PMID:19739117
Shi W, Alajez NM, Bastianutto C, Hui AB, Mocanu JD, Ito E, Busson P, Lo KW, Ng R, Waldron J, Sullivan BO, Liu FF.
Int J Cancer. 2009 Sep 8. [Epub ahead of print]

 

 
 
 
  miRBase
  Tarbase
  miRGen
  miRGator
  CCBB
  MicroRNA.org
  miRRim
  miRNAMap 2.0
 
 
Please don't hesitate to address comments/questions/suggestions regarding this webpage to: ydwang@hit.edu.cn or yunliu@iu.edu