title: Upregulation of miR-136 in human non-small cell lung cancer cells promotes Erk1/2 activation by targeting PPP2R2A.
abstract: MicroRNAs (miRNAs) have been integrated into cancer development and progression, because they repress translation of target genes which can be tumor suppressors and oncogenes. A number of miRNAs have been found to be closely related to human non-small cell lung cancer (NSCLC). However, the roles of miR-136 in NSCLC are still largely unknown. Here, we show that miR-136 is significantly upregulated in human NSCLC primary tumors and cell lines compared to their nontumor counterparts. Suppression of miR-136 expression in NSCLC cell line A549 inhibited both anchorage-dependent and anchorage-independent proliferation. Further studies showed that suppression of miR-136 expression attenuated phosphorylation of extracellular-signal-regulated kinase 1/2 (Erk1/2). We found that serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B α isoform (PPP2R2A, also known as B55α) was a direct target of miR-136, and suppression of miR-136 expression led to a robust increase in both mRNA and protein levels of PPP2R2A. We found that miR-136 promoted phosphorylation of Erk1/2 through inhibition of PPP2R2A expression, and forced overexpression of PPP2R2A abrogated promotion of Erk1/2 phosphorylation by miR-136. Moreover, forced overexpression of PPP2R2A abrogated the promoting effect of miR-136 on cell growth and led to a reduced growth rate of NSCLC cells. Our findings indicate that miR-136 promotes Erk1/2 phosphorylation through targeting PPP2R2A in NSCLC cells and suggest that it may serve as a therapeutic target in NSCLC therapy.
authors: Sining
authors: S
authors: Shen
authors: Han
authors: H
authors: Yue
authors: Yin
authors: Y
authors: Li
authors: Jianjun
authors: J
authors: Qin
authors: Ke
authors: K
authors: Li
authors: Ying
authors: Y
authors: Liu
authors: Jiaxiang
authors: J
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D020029:Base Pairing; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: C577037:MIRN136 microRNA, human; D035683:MicroRNAs; C512974:PPP2R2A protein, human; D054648:Protein Phosphatase 2
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