Long non-coding ROR promotes the progression of papillary thyroid carcinoma through regulation of the TESC/ALDH1A1/TUBB3/PTEN axis

Abstract

Papillary thyroidal carcinoma (PTC) is a common endocrine cancer that plagues people across the world. The potential roles of long non-coding RNAs (lncRNAs) in PTC have gained increasing attention. In this study, we aimed to explore whether lncRNA ROR affects the progression of PTC, with the involvement of tescalcin (TESC)/aldehyde dehydrogenase isoform 1A1 (ALDH1A1)/βIII-tubulin (TUBB3)/tensin homolog (PTEN) axis. PTC tumor and adjacent tissues were obtained, followed by measurement of lncRNA ROR and TESC, ALDH1A1, and TUBB3 expression. Interactions among lncRNA ROR, TESC, ALDH1A1, TUBB3, and PTEN were evaluated by ChIP assay, RT-qPCR, or western blot analysis. After ectopic expression and depletion experiments in PTC cells, MTT and colony formation assay, Transwell assay, and flow cytometry were performed to detect cell viability and colony formation, cell migration and invasion, and apoptosis, respectively. In addition, xenograft in nude mice was performed to test the effects of lncRNA ROR and PTEN on tumor growth in PTC in vivo. LncRNA ROR, TESC, ALDH1A1, and TUBB3 were highly expressed in PTC tissues and cells. Overexpression of lncRNA ROR activated TESC by inhibiting the G9a recruitment on the promoter of TESC and histone H3-lysine 9me methylation. Moreover, TESC upregulated ALDH1A1 expression to increase TUBB3 expression, which then reduced PTEN expression. Overexpression of lncRNA ROR, TESC, ALDH1A1 or TUBB3 and silencing of PTEN promoted PTC cell viability, colony formation, migration, and invasion while suppressing apoptosis. Moreover, overexpression of lncRNA ROR increased tumor growth by inhibiting PTEN in vivo. Taken together, the current study demonstrated that lncRNA ROR mediated TESC/ALDH1A1/TUBB3/PTEN axis, thereby facilitating the development of PTC.

LINC01305 recruits basonuclin 1 to act on G‐protein pathway suppressor 1 to promote esophageal squamous cell carcinoma

“…34 In the present study, we identified the transcription factors GRHL2 and BNC1 to be highly expressed A number of studies have shown that transcription factors bind to lncRNAs to promote tumor development. [21][22][23]35 Thus, we found that LINC01305 and BNC1 were specifically bound using RIP assay and RNA pull-down assay.…”

“…At present, a large number of studies have reported that transcription factors do not act as protein forms alone for their transcriptional function, generally by binding lncRNAs to form transcriptional complexes acting on target genes and regulating the expression of downstream target genes 21–24 . We hypothesized that BNC1 might bind to lncRNAs to form a transcriptional complex to promote the expression of downstream target genes, based on the above reports and scenarios.…”

“…More studies have shown that BNC1 is closely related to the occurrence of tumors, and BNC1 is upregulated by the transcription factor tumor protein P63 (TP63) in head and neck squamous cell carcinoma 19 and highly expressed by Gli protein in basal cell carcinoma 20 . Research has shown that transcription factors could not function in the process as protein forms alone, and they usually bind with lncRNAs to control the transcription of target genes 21–24 . But whether BNC1 plays its role in binding to lncRNAs in ESCC is unknown.…”

ALDH1: A potential therapeutic target for cancer stem cells in solid tumors

“…Studies have shown that in HNCs, ALDH1 is mainly regulated by retinoic acid compounds and other oncogenic pathways such as MUC1-C/ERK and WNT/b-catenin (191), but also by the AKT signaling pathway (192,193). ALDH1A1 increases TUBB3 expression, which down-regulates PTEN and promotes cell proliferation, migration, and invasion (194).…”

“…Studies have shown that in HNCs, ALDH1 is mainly regulated by retinoic acid compounds and other oncogenic pathways such as MUC1-C/ERK and WNT/β-catenin ( 191 ), but also by the AKT signaling pathway ( 192 , 193 ). ALDH1A1 increases TUBB3 expression, which down-regulates PTEN and promotes cell proliferation, migration, and invasion ( 194 ). Inhibition of miR-30a and miR-379 upregulates DNMT3B expression, which leading to hypermethylation of the ALDH1A gene, and promotes oncogenic activity ( 195 , 196 ).…”