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2015 ; 13
(ä): 105
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Let-7a inhibits migration, invasion and epithelial-mesenchymal transition by
targeting HMGA2 in nasopharyngeal carcinoma
#MMPMID25884389
Wu A
; Wu K
; Li J
; Mo Y
; Lin Y
; Wang Y
; Shen X
; Li S
; Li L
; Yang Z
J Transl Med
2015[Mar]; 13
(ä): 105
PMID25884389
show ga
BACKGROUND: Let-7a has been shown to play important roles in nasopharyngeal
carcinoma (NPC) cell proliferation and apoptosis, but little is known about the
function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed
to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma
metastasis and clarified the regulation of high mobility group A2 (HMGA2) by
let-7a. METHODS: The expression levels of let-7a and HMGA2 were examined in NPC
clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2
was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR,
and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating
NPC cells biological properties including proliferation, migration, invasion and
epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics
and si-HMGA2 transfected cells. RESULTS: Our study demonstrated that let-7a was
downregulated and inversely associated with the clinical stage, T classification
and N classification, and HMGA2 was upregulated and directly associated with the
clinical stage and N classification in patients with NPC. Moreover, there was an
inverse correlation between let-7a expression and HMGA2 expression in NPC
patient. In addition, HMGA2 was negatively regulated at the posttranscriptional
level by let-7a via a binding site of HMGA2-3'UTR. In addition, synthetic let-7a
mimics suppressed NPC cells migration, invasion and EMT process and knockdown of
HMGA2 was consistent with the effects of let-7a in NPC cells. CONCLUSION: Let-7a
directly downregulates HMGA2 protein expression, which suppress NPC cell
migration, invasion and EMT process. Let-7a could serve as a potential diagnostic
marker and therapeutic target for NPC.