title: Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.
abstract: The role of microRNA-155 (miR-155) has been associated with oncogenesis of several human tumors. However the expression pattern of miR-155 has not been investigated in nasopharyngeal carcinoma (NPC). The present study was to assess miR-155 expression pattern and its possible function in NPC, to identify its targets and evaluate their clinical applications in NPC. MiR-155 was found to be upregulated in two Epstein-Barr virus (EBV) negative NPC derived cell lines CNE1 and TW03, as well as in NPC clinical samples by quantitative Real-time PCR and in situ hybridization detection. EBV encoded LMP1 and LMP2A could further enhance the expression of miR-155 in NPC CNE1 and TW03 cells. JMJD1A and BACH1 were identified as putative targets of miR-155 in a bioinformatics screen. Overexpression of miR-155 downregulated a luciferase transcript fused to the 3'UTR of JMJD1A and BACH1. MiR-155 mimic could downregulate the expression of JMJD1A and BACH1, while miR-155 inhibitor could upregulate JMJD1A expression in NPC cell lines. Moreover, downregulation of JMJD1A was significantly correlated with N stage in TNM classification (p = 0.023), a lower five-year survival rate (p = 0.021), and a lower five-year disease-free survival rate (p = 0.049) of NPC patients. Taken together, up-regulation of miR-155 in NPC is partly driven by LMP1 and LMP2A, and results in downregulation of JMJD1A, which is associated with N stage and poor prognosis of NPC patients. The potential of miR-155 and JMJD1A as therapeutic targets in NPC should be further investigated.
authors.affiliation: State Key Laboratory of Oncology in South China, and Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Zi-Ming
authors.initials: ZM
authors.lastname: Du
authors.forename: Li-Fu
authors.initials: LF
authors.lastname: Hu
authors.forename: Hai-Yun
authors.initials: HY
authors.lastname: Wang
authors.forename: Li-Xu
authors.initials: LX
authors.lastname: Yan
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Ingemar
authors.initials: I
authors.lastname: Ernberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015854:Up-Regulation / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D051856:Fanconi Anemia Complementation Group Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D014763:Viral Matrix Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C530247:KDM3A protein, human