LOXL1‑AS1 promotes thymoma and thymic carcinoma progression by regulating miR‑525‑5p‑HSPA9.

Abstract

Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the present study was to explore the mechanism by which the long noncoding RNA (lncRNA) LOXL1-AS1 affects thymoma and thymic carcinoma progression by targeting the miR-525-5p-HSPA9 axis. Bioinformatics was used to analyse the process of LOXL1-AS1 targeting miR-525-5p-HSPA9 and its expression characteristics in TET. The relationships between LOXL1-AS1, miR-525-5p, HSPA9 and prognosis were analysed. The dual luciferase reporter assay was applied to verify targeting. The gene was knocked down or overexpressed by plasmid transfection. Cell counting kit 8 (CCK-8) assay, flow cytometry and Transwell assay were used to detect cell viability, apoptosis and invasion ability, respectively. Proteins and RNAs were examined by western blot analysis and qPCR, respectively. A tumour-burdened assay was used to perform in vivo verification. LOXL1-AS1 and HSPA9 were overexpressed in thymoma and thymic carcinoma; high levels of LOXL1-AS1 and HSPA9 were associated with poor prognosis, and there was a significant positive correlation between their levels. Downregulation of miR-525-5p expression was also associated with poor prognosis of patients. Clinical trials also demonstrated the same trends. miR-525-5p inhibited the expression of HSPA9 protein by targeting the 3′-untranslated region (UTR) of HSPA9 mRNA. LOXL1-AS1 promoted the expression of HSPA9 as a sponge targeting miR-525-5p. Animal experiment results also showed that knockdown of miR-525-5p promoted cancer by promoting the expression of HSPA9. In conclusion, LOXL1-AS1 and HSPA9 are highly expressed in thymoma and thymic carcinoma; miR-525-5p is expressed at low levels in thymoma and thymic carcinoma; and downregulation of miR-525-5p is associated with poor prognosis. In summary, this study demonstrates that LOXL1-AS1 acts as a sponge that targets miR-525-5p to promote HSPA9 expression, thereby promoting the growth and invasion and inhibiting apoptosis of thymoma and thymic carcinoma cells.