Nuclear Factor-κB Contributes to Anaplastic Thyroid Carcinomas through Up-Regulation of miR-146a

Abstract

Our results show that NF-kappaB contributes to anaplastic thyroid cancer up-regulating the expression of miR-146a.

MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology

“…The miR-146 family, miR-146a and miR-146b , is overexpressed in ATC [18, 29, 48]. Despite sharing the same seed region, and therefore targets, miR-146a and miR-146b are transcribed by two independent genes located on chromosomes 5 and 10, respectively, and regulated by the transcription factor NF κ B.…”

“…The promoter region of both miRNAs contains binding sites for the NF κ B complex, part of a key oncogenic signaling pathway, usually overactivated in ATC, which shows increased nuclear staining for RelA (p65), the subunit of the NF κ B dimer [49]. Ectopic expression of the inhibitory protein of this signaling, I κ B, decreases miR-146a and miR-146b levels in an ATC cell line [48]. Moreover, inhibition of miR-146a leads to an abrogation of anchorage-independent growth and invasion by ATC cells [48].…”

“…Ectopic expression of the inhibitory protein of this signaling, I κ B, decreases miR-146a and miR-146b levels in an ATC cell line [48]. Moreover, inhibition of miR-146a leads to an abrogation of anchorage-independent growth and invasion by ATC cells [48]. Interestingly, NF κ B activation is observed at the invasive front of aggressive PTC showing local invasion compared to the central region of the tumor [50] and also in response to a BRAF V600E oncogene, leading to cell migration and invasion [51], and miR-146b upregulation [52].…”

Cancer stem-like cells and thyroid cancer

“…miR-146a was also shown to be upregulated in ATCs. The inhibition of miR-146a expression in the FRO ATC cell line decreased their oncogenic potential and increased the susceptibility to chemotherapeutic drug-induced apoptosis (Pacifico et al 2010). miR-146a was identified as a common target of Krüppel-like factor 8 (KLF8) and TGFb, both of which are known EMT-inducers in breast cancer cell line (Wang et al 2013).…”

Human rpL3 induces G₁/S arrest or apoptosis by modulating p21waf1/cip1 levels in a p53-independent manner

“…Cell cycle analysis, BrdU (5'-Bromo-2'-deoxyuridine) incorporation and tetramethylrhodamine ethyl ester (TMRE) staining were performed as previously reported. 46,47 Samples were analyzed by a CyAn ADP Flow Cytometer (DAKOCytomation) and quantified using Summit Software.…”