@Article{or.2025.068313,
AUTHOR = {Yingjie Wang, Wanlin Dong, Can Wang, Zirui Li, Yongqiang Wang, Qi Li, Cheng-Ya Dong},
TITLE = {Long Non-Coding RNA HOXA10-AS Promotes the Migration and Invasion of Glioblastoma Cells by Serving as a Competing Endogenous RNA for miR-99a-3p to Upregulate ITGB5 Expression},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {12},
PAGES = {4093--4111},
URL = {http://www.techscience.com/or/v33n12/64633},
ISSN = {1555-3906},
ABSTRACT = { <b>Objectives:</b> Glioblastoma is a prevalent malignant brain tumor, and the actions of the long non-coding RNA HOXA10-AS in its invasion and migration remain unclear. Here, the function of HOXA10-AS in glioblastoma cell invasion and migration and associated mechanisms were investigated. <b>Methods:</b> HOXA10-AS was knocked down in glioblastoma cells, and Transwell and wound healing assays were conducted to elucidate its impacts on cell invasion and migration. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assessed HOXA10-AS’s impact on the epithelial-mesenchymal transition (EMT). Microarray analysis identified differentially expressed genes, complemented by bioinformatics approaches to explore potential molecular participants and pathways. Rescue experiments validated our findings. <b>Results:</b> HOXA10-AS knockdown significantly inhibits glioblastoma cell migration, invasion, and the EMT process. Specifically, HOXA10-AS siRNA transfection significantly reduced the migratory capacity of A172 cells by 50.5% and U251 cells by 61.4%, as well as their invasive capacities by 33.8% and 58.5%, respectively (all <i>p</i> < 0.05). HOXA10-AS acts as an miR-99a-3p sponge, and pathway analysis identified processes linked to tumorigenesis and metastasis, along with nine hub genes. HOXA10-AS upregulates the expression of integrin subunit beta 5 (ITGB5) through a competing endogenous RNA mechanism. The reduced tumorigenic behavior of glioblastoma cells due to HOXA10-AS knockdown can be rescued by ITGB5 overexpression or miR-99a-3p inhibitor. <b>Conclusion:</b> These results indicate that HOXA10-AS promotes tumorigenic behavior in glioblastoma cells by regulating the EMT-like process and functioning as an miR-99a-3p sponge to modulate ITGB5 levels, providing insights into glioblastoma development and potential therapeutic targets.},
DOI = {10.32604/or.2025.068313}
}