LncRNA TMPO-AS1 facilitates cervical cancer cell tumorigenesis and ferroptosis resistance via interaction with LCN2.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, has demonstrated anti-tumor properties in multiple malignancies. Long non-coding RNAs play a crucial role in the tumorigenesis and progression of cervical squamous cell cancer; however, the mechanisms underlying the actions of many lncRNAs in ferroptosis remain elusive. Here, the expression level of LICN-TMPO-AS1 in CESC was detected using quantitative real-time polymerase chain reaction. Loss- and gain-of-function experiments with TMPO-AS1 were performed using the CCK-8 assay, transwell assays, clone formation assays, and xenograft models. The relationship between TMPO-AS1, Lipocalin 2, and SFPQ were identified and validated by RNA pull-down/mass spectrometry, co-immunoprecipitation, RNA immunoprecipitation (RIP) assay and western blotting. We found that TMPO-AS1 expression was frequently upregulated in CESC tissues and cells and was strongly associated with poor prognosis. TMPO-AS1 decreased the lipid reactive oxygen species, intracellular Fe(2+), and malondialdehyde content, leading to the inhibition of sulfasalazine- and erastin-induced ferroptosis. Overexpression of TMPO-AS1 weakened the anti-tumor sensitivity to sulfasalazine by inhibiting ferroptosis both in vitro and in vivo. Mechanistically, TMPO-AS1 bound LCN2 and activated LCN2 expression. Targeting LCN2 reduced iron accumulation and ROS generation in Siha cells. Furthermore, LCN2 regulated the expression of solute carrier family 7 member 11 by interacting with the splicing factor proline and glutamine-rich. Our study illustrates that TMPO-AS1 functions as a tumorigenic regulator and may be a promising therapeutic target for CESC patients with high TMPO-AS1 expression.