title: MicroRNA-146a targets PRKCE to modulate papillary thyroid tumor development.
abstract: MicroRNAs are single-stranded noncoding RNAs composed of approximately 22 nucleotides that suppress gene expression by selectively binding via base-pairing to the complementary 3'-untranslated region (3'-UTR) of messenger RNA transcripts. Protein kinase C epsilon (PKCε) is an important modulating member of the transducing Ras/Raf-1 signal pathway; a computational search revealed miR-146a putatively binds to the 3'-UTR of the PRKCE gene, and thus decreasing PKCε expression. Moreover, PKCε inhibits mitochondrial apoptosis and is associated with the Bcl family. However, it has been previously reported that miR-146a expression in papillary thyroid carcinoma (PTC) is slightly elevated. Thus, we hypothesized that because miR-146a expression depends on nuclear factor kappaB (NF-κB) activation and NF-κB expression is elevated in PTC, miR-146a is potentially upregulated in PTC via negative feedback of NF-κB, and thus suppressing PKCε expression. In our study, we investigated whether overexpression of miR-146a, a tumor-suppressing-miR, in PTC cells decreases cell survival and induces apoptosis. Luciferase reporter assay analysis confirmed the direct binding of miR-146a and PRKCE 3'-UTR. Specific overexpression of exogenous miR-146a significantly decreased PKCε levels in PTC cell line NPA-187 and increased apoptosis. Additionally, using stably expressing miR-146a thyroid carcinoma cells to establish subcutaneous tumors, the tumor growth exhibited significant inhibition. Our study confirmed the tumor-suppressing role of miR-146a in thyroid carcinoma cells and contributes to the knowledge regarding modulation of Ras/Raf-1 signal transduction and apoptosis via PKCε targeted by miR-146a in PTC; moreover, our findings confirmed that miR-146a is involved in the feedback system of the classical NF-κB signal pathway in PTC.
authors: Department of Nuclear Medicine, Shanghai 10th People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
authors: Xiaoping
authors: X
authors: Zhang
authors: Dan
authors: D
authors: Li
authors: Maoquan
authors: M
authors: Li
authors: Meng
authors: M
authors: Ye
authors: Lanbao
authors: L
authors: Ding
authors: Haidong
authors: H
authors: Cai
authors: Da
authors: D
authors: Fu
authors: Zhongwei
authors: Z
authors: Lv
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D019908:Proto-Oncogene Proteins c-raf; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon; D018631:ras Proteins
keywords: MicroRNA-146a; NF-kB; PRKCE; papillary thyroid tumor