Published on Jan. 22, 2017 in Biochem Biophys Res Commun volume 482(4).

PubMed ID: 27856248

DOI: S0006-291X(16)31933-7


Abstract:

Methyltransferase like 3 (METTL3) was incipiently known as a methyltransferase whichwas responsible for N(6)-methyladenosine (m(6)A) methylation. METTL3 can promote theexpression of several crucial oncoproteins and its high expression enhancedproliferation, survival, and invasion of human lung cancer cells. However, howMETTL3 was regulated is seldom understood in non-small-cell lung carcinoma (NSCLC).In the present study, miR-33a was suspicious to target to the 3'-untranslated region(3'UTR) of METTL3 mRNA via in silico prediction. Besides, the expressions of METTL3were higher in NSCLC tissues than those in adjacent tissues, and METTL3 expressionswere positively related to the expressions of miR-33a in NSCLC tissues whichconfirmed by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-33a candirectly target to the 3'UTR of METTL3 mRNA which examined by luciferase reportergene assay. Moreover, we found that miR-33a can reduce the expression of METTL3 atboth mRNA and protein levels using reverse transcription-polymerase chain reaction(RT-PCR) and Western blot analysis. Functionally, miR-33a can reduce theproliferation of A549 and NCI-H460 cells. Conversely, inhibition of miR-33a byanti-miR-33a can rescue that using4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and5-ethynyl-2-deoxyuridine (EdU) assay. Similarly, miR-33a can reduce cellularanchorage-independent growth of A549 cells. Additionally, the negative influences ofmiR-33a on the downstream genes of METTL3 were examined by Western blot analysis.Thus, we concluded that miR-33a can attenuate NSCLC cells proliferation viatargeting to the 3'UTR of METTL3 mRNA. Our findings provide new insights into themechanism of METTL3 regulation by micro RNA, and supports METTL3 as a therapeutictarget in NSCLC.CI - Copyright © 2016 Elsevier Inc. All rights reserved.



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