GRC NPC – Liu, Fei-Fei

Fei-Fei Liu (Princess Margaret Hospital, Canada)
“Prognostic Significance of miRNA Signatures for Detection of Metastatic NPC”

• metastatic NPC, metastamirs   let-7  miR9
• Nanostring 654 miRNA + 34 EBV mi RNA +   mi RNA from other viruses on 124 patients
• Bruce Oncotarget , 2015 miRNAS 154 + miRNA 449 – MENA 140 – MIRNA 34c (Bruce et al., Oncotarget, 2015)
• N stage coefficient 0.3 p – value very significant
• Adding LN status to miRNA signature
• However, no miRNA signatures overlaps with those in Liu et al (Liu et al., Lancet Oncol, 2012 馬駿group)  
• ———–以下未發表
• Cell line data NP69 NP460 C666-1     miR-499  pops out
• KO of more 499  73 downregulated ones top 1 is TGFBI
• CO-IP OF ITGB3 and TGFBI (also expressed into media)
• miRNA in TME!!
• Also exsomal miRNA in metastatic niche
• CD9, FLOT1

From Ming-Han

• @Some miRNA levels highly associated to tumorigenesis (white et al, Nature review clinical oncology 8:75 2014)
• @FFPE->microdissection-> RNA kit-> sequence.
• @654 hmiRNA; 34EBV miRNAs had been detect
• @normal NPE cell as control.
• @use combined calculation to calculate:
• miR154*0.147+mir449b*0.28-mir34C*0.311-miR140*0.653 (if value is high: high risk of relapse!!)
• (Bruce et al: oncotarget 6: 4537 2015yr).
• Especially mir449b and miR34C highly expressed in EBV+ NPC cell line.
• @Mechanisms: KD of miR34C or mir449b can make C666 sensitive to Cisplatin. (C666 doesn’t affair Cisplatin!)
• What’s the target?? TGFBI
• 
  
• Tumor repression
• Low TFGBI consistent to promoter methylation
• TGFBI KO mice: no tumor.
• tf TGFBI into C666: become sensitive to cisplatin.
• KD TGFBI into NP69: resistant to cisplatin.
• Use 293 IP-> flag TGFBI-> pull down ITGB3.
• TGFBI is secreting protein.
• Model: TGFBI bind to ITGB3-> Block PTEN
• TGFB-> induce PI3K—> PI3Kp-> resistant to cisplatin