DNMT1/DNMT3a-mediated promoter hypermethylation and transcription activation of ICAM5 augments thyroid carcinoma progression.

Promoter methylation is one of the most studied epigenetic modifications and it is highly relevant to the onset and progression of thyroid carcinoma (THCA). This study investigates the promoter methylation and expression pattern of intercellular adhesion molecule 5 (ICAM5) in THCA. CpG islands with aberrant methylation pattern in THCA, and the expression profiles of the corresponding genes in THCA, were analyzed using bioinformatics. ICAM5 was suggested to have a hypermethylation status, and it was highly expressed in THCA tissues and cells. Its overexpression promoted proliferation, mobility, and tumorigenic activity of THCA cells. As for the downstream signaling, ICAM5 was found to activate the MAPK/ERK and MAPK/JNK signaling pathways. Either inhibition of ERK or JNK blocked the oncogenic effects of ICAM5. DNA methyltransferases 1 (DNMT1) and DNMT3a were found to induce promoter hypermethylation of ICAM5 in THCA cells. Knockdown of DNMT1 or DNMT3a decreased the ICAM5 expression and suppressed malignant properties of THCA cells in vitro and in vivo, which were, however, restored by further artificial ICAM5 overexpression. Collectively, this study reveals that DNMT1 and DNMT3a mediates promoter hypermethylation and transcription activation of ICAM5 in THCA, which promotes malignant progression of THCA through the MAPK signaling pathway.

Transcription Factor E2F1 Exacerbates Papillary Thyroid Carcinoma Cell Growth and Invasion via Upregulation of LINC00152.

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid neoplasm, whereas transcription factor E2F1 has been previously implicated in PTC progression. The current study sought to elucidate the underlying mechanism of E2F1 in PTC cell biological activities via regulation of long intergenic noncoding RNA 152 (LINC00152). Methods: Firstly, the expression patterns of LINC00152 and E2F1 in PTC were determined. Besides, TPC-1 and IHH-4 cells were adopted to carry out a series of experiments. Cell proliferation was detected by means of a cell counting kit-8 assay and colony formation assay, while cell migration and invasion abilities were assessed using a Transwell assay. Next, the interaction between E2F1 and LINC00152 was certified. Lastly, xenograft transplantation was carried out to validate the effects of E2F1 depletion on PTC. Results: Both LINC00152 and E2F1 were highly expressed in PTC cells. Knockdown of LINC00152 led to reduced cell activity, while LINC00152 overexpression brought about the opposing trends. Likewise, E2F1 knockdown quenched cell proliferation, migration, and invasion. However, the combination of E2F1 knockdown and LINC00152 overexpression resulted in augmented cell growth. In addition, E2F1 induced LINC00152 overexpression, which accelerated cell proliferation, migration, and invasion by activating the PI3K/AKT axis, whereas the administration of LY294002, the inhibitor of PI3K, led to reversal of the same. Finally, xenograft transplantation validated that E2F1 inhibition could suppress LY294002, thereby discouraging tumor growth. Conclusion: Our findings highlighted that E2F1 augmented PTC cell proliferation and invasion by upregulating LINC00152 and the PI3K/AKT axis. Our discovery provides therapeutic implications for PTC alleviation.