Objective:The study was aim to investigate the effect of HOX transcript antisense RNA (HOTAIR) on the growth, migration, and invasion of papillary thyroid carcinoma (PTC) and its underlying mechanisms.Methods:Cell growth, invasion, and migration was respectively investigated using the MTT assay, trans-well assay, and wound healing assay. The expression of genes and proteins was respectively determined by Western blot analysis and RT-PCR experiments.Results:It was demonstrated that high expression of HOTAIR in PTC cells (BCPAP) and tissues resulted in fast tumor growth and poor survival time of the PTC-bearing mice models. Moreover, overexpression of HOTAIR leaded to markedly enhanced proliferation, migration, and invasion of BCPAP cells. Increase the levels of HOTAIR in BCPAP cells signally down-regulated the miR-488-5p levels which was able of inhibiting the growth rate, increasing the apoptosis rate, and decreasing the invasion/migration ability of BCPAP cells. Further studies indicated that HOTAIR promoted BCPAP cell growth, invasion, and migration mainly through regulating the miR-488-5p/NUP205 axis and the levels of Bcl-2 as well.Conclusion:HOTAIR promoted the growth, migration, and invasion of papillary thyroid carcinoma mainly through regulating the miR-488-5p/NUP205 axis.
Background Hepatocellular carcinoma (HCC) is a lethal malignancy driven by cancer stem cells, which drive progression and therapeutic resistance. Nuclear pore protein ELYS is implicated in tumorigenesis, but its role in HCC stemness remains unclear. Methods Transcriptome sequencing identified ELYS-induced differentially expressed genes (DEGs). Functional impacts of ELYS on malignant phenotypes and stemness were assessed in vitro. Signaling pathway activation was confirmed using inhibitors of Hedgehog (GANT-61) and AKT (MK-2206 2HCl). Bioinformatics analysis, luciferase reporter, and ChIP assays elucidated the FOXO6-NUP205 axis. Xenograft models validated the findings in vivo. Clinical relevance was evaluated using TCGA-HCC data and immunohistochemistry in clinical samples. Results DEGs in ELYS-overexpressing cells were enriched in PI3K/AKT and Hedgehog (Hh) pathways. ELYS facilitated Gli-1 nuclear translocation by activating PI3K/AKT, placing it upstream of Hh. Bioinformatic and experimental analyses identified FOXO6 and its target NUP205 as key effectors. ELYS upregulated FOXO6, which directly activated NUP205 transcription. FOXO6 knockdown suppressed ELYS-induced effects on NUP205, Gli-1 nuclear translocation, and stemness factors. In vivo, ELYS promoted tumor growth and lung metastasis via PI3K/AKT/Hh. Clinically, ELYS, FOXO6, and NUP205 were overexpressed in HCC, correlating with advanced features and poor survival. Conclusion This study defines an oncogenic axis wherein ELYS promotes HCC stemness and metastasis by activating PI3K/AKT, triggering a FOXO6-NUP205 cascade to drive Hedgehog, representing a pivotal mechanism and therapeutic target. Graphical abstract
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