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

Abstract

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.

The specific regulatory networks between different variants in papillary thyroid carcinoma: A transcriptomics study

“…The E2F1 pathway is essential for controlling the expression of genes in the G1/S phase 10,11 . We also found that E2F1 is an important speci c factor in PTC, which was similar to the ndings of a study by Yang et al 12 . We also identi ed E2F1 as a possible transcriptional target, which might be associated with an imbalance in the mechanism of the cell cycle in cancer cells.…”

Identification of novel immune-related molecular subtypes and a prognosis model to predict thyroid cancer prognosis and drug resistance

“…Alterations in Claudin-2 ( CLDN2 ), a component of cellular tight junction, are involved in the progression of a variety of cancer types ( Buchert et al, 2010 ; Tabariès et al, 2011 ; Tabariès et al, 2012 ). E2F1 is a potent oncogene in human cancers, including thyroid cancer, prostate cancer, lung cancer, and colorectal cancer, that can accelerate the invasion, spread, and metastasis of cancer cells and further predict poor prognosis ( Bi et al, 2017 ; Yin et al, 2017 ; Zhou et al, 2020 ; Yang et al, 2022 ).…”

Increased expression and immune cell infiltration of E2F1/2 collerate with better prognosis in thyroid cancer

“…Zhang et al [24] stated that E2F1 could facilitate the transcription of lncRNA RGMB-AS1 by binding to its promoter region, promoting proliferation, invasion, and migration of thyroid cancer cells. Yang et al [25] reported that E2F1 augments thyroid cancer cell proliferation and invasion by upregulating LINC00152 and the PI3K/AKT axis. Yi et al [26]found that overexpressing E2F2 could promote the proliferation, migration, invasion and epithelial-mesenchymal transition of thyroid cancer cell via the E2F2/TNIK Axis.…”