LncRNA HOTTIP facilitates cell proliferation, invasion, and migration in osteosarcoma by interaction with PTBP1 to promote KHSRP level

This study designs to investigate the role and potential mechanism of lncNRA HOTTIP in OS progression in vitro and in vivo. HOTTIP, PTBP1, and KHSRP expression levels were tested through qRT-PCR and western blot in OS tissues or cell lines. Cell proliferation was examined via CCK-8 and colony formation. Cell cycle and apoptosis were analyzed via flow cytometry analysis. The invasive and migratory abilities of OS cells were evaluated by transwell and wound-healing assays. The localization of HOTTIP in OS cells was determined by subcellular fractionation assay. RNA pull down and RNA immunoprecipitation were allowed to assess the interaction between HOTTIP and PTBP1. Xenograft tumor growth assay was employed to test the role of HOTTIP and KHSRP in OS progression. Our data demonstrated HOTTIP was upregulated in OS tissues. HOTTIP knockdown resulted in a suppression of OS cell proliferation, invasion and migration, as well as a promotion of OS cell apoptosis, while HOTTIP overexpression exhibited opposite effects. In mechanism, PTBP1 and KHSRP highly expressed in OS and HOTTIP was identified to interact with PTBP1 to promote KHSRP expression. Meanwhile, we found that overexpression of KHSRP or PTBP1, individually, can partially remove the repression of HOTTIP suppression for OS cell progression. Moreover, xenograft tumor growth assay revealed that HOTTIP knockdown significantly inhibited tumor growth, and this inhibitory effect was abolished by KHSRP overexpression. Collectively, these findings confirmed that HOTTIP facilitates OS cell proliferation, invasion and migration by binding to PTBP1 to promote KHSRP level.

Automated summary

This study discovered that HOTTIP promotes proliferation, invasion, and migration of OS cells by binding to PTBP1 to enhance KHSRP levels. Additionally, the inhibitory effects of HOTTIP overexpression can be partially counteracted by overexpression of KHSRP or PTBP1.