hnRNPA2B1介导 m6A 修饰MIR100HG促进胃癌MKN-28细胞增殖和侵袭作用

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【中图分类号】R56

【文献标志码】A

【Abstract】Objective :To investigate the expression of N6 -methyladenosine( m6A )reader heterogeneous nuclear ribonucleoprotein A2/

B1(hnRNPAB1)inhumangastriccancer(GC)tissueanditseffectontheproliferationandinvasionofMKN-28cells.Methods:he

Cancer Genome AtlasandGene Expresson Omnibus wereusedtoanalyze theexpressonofhnRNPA2B1andlong noncoding RNA(ln

cRNA)mir-100-let-7a-2-mir-125b-1clusterhostgene(MIR100HG)inGCtissueandtheirassociationwiththeclinicalprognosis

of patients with GC.QuantitativePCRand Westernblotingwereused to measuretheefectofhnRNPA2Blontheexpressonlevelof

MIR10OHGanditsdownstreamWnt/β-cateninsignaling pathway;MethylatedRNAimmunoprecipitation(MeRIP)wasusedtomea

sure the m6A levelofMIR1OoHG;CCK-8 assayand Transwellassay were usedtoobserve cellproliferationand invasion.Results :Com

paredwith paracancerous tissue,human GC tissueshowed significant increases in theexpression levelsof hnRNPA2B1( t=6.101,P< (204号

0.001)and MIR100HG( t=2.191 P=0.036 7 ),and the high expression levels of hnRNPA2B1 and MIR1OoHG were associated with

poorsurvivalinpatients withGC.KnockdownofhnRNPA2B1reducedthemRNAexpresionlevel(t=5.156,P=0.007)andmAlevel

of MIR100HG(t=4.789, P =0.010),inhibited the proliferation and invasion of MKN-28 cells( t=4.915 ,P=0.008 and t=5.167,P= 0.007),and blocked the activity of the Wnt/β -catenin signaling pathway( P <0.05). Overexpression of MIR100HG promoted cell proliferation andinvasion( t= 3.578, P =0.023and τ =8.411, P =0.001), activated theWnt/β-catenin signaling pathway( P <0.01),and reversedthe antitumor effectinducedby hnRNPA2B1knockdown( t=3.667 P=0.021 ).Conclusion:This study shows that hnRNPA2B1- mediatedm6Amodificationof MIR10oHG promotes the proliferationand invasionofGCMKN-28cellsbyactivatingtheWnt/B -catenin signaling pathway.

【Key words】heterogeneous nuclear ribonucleoprotein A2/B1;gastric cancer;proliferation

胃癌是最常见的胃肠道恶性肿瘤之一,在全球范围内发病率排第5,癌症相关死亡率排第 3[1] 。(剩余9300字)

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