Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer

Background: Pyroptosis and prostate cancer (PCa) are closely related. The role of pyroptosis-related long non-coding RNAs (lncRNAs) (PRLs) in PCa remains elusive. This study aimed to explore the relationship between PRL and PCa prognosis.

Methods: Gene expression and clinical signatures were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A PRL risk prediction model was established by survival random forest analysis and least absolute shrinkage and selection operator regression. Functional enrichment, immune status, immune checkpoints, genetic mutations, and drug susceptibility analyses related to risk scores were performed by the single-sample gene set enrichment analysis, gene set variation analysis, and copy number variation analysis. PRL expression was verified in PCa cells. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, transwell, and Western blotting assay were used to detect the proliferation, migration, invasion, and pyroptosis of PCa cells, respectively.

Results: Prognostic features based on six PRL (AC129507.1, AC005253.1, AC127502.2, AC068580.3, LIMD1-AS1, and LINC01852) were constructed, and patients in the high-score group had a worse prognosis than those in the low-score group. This feature was determined to be independent by Cox regression analysis, and the area under the curve of the 1-, 3-, and 5-year receiver operating characteristic curves in the testing cohort was 1, 0.93, and 0.92, respectively. Moreover, the external cohort validation confirmed the robustness of the PRL risk prediction model. There was a clear distinction between the immune status of the two groups. The expression of multiple immune checkpoints was also reduced in the high-score group. Gene mutation proportion in the high-score group increased, and the sensitivity to drugs increased significantly. Six PRLs were upregulated in PCa cells. Silencing of AC005253.1 inhibited cell proliferation, migration, and invasion in DU145 and PC-3 cells. Moreover, silencing of AC005253.1 promoted pyroptosis and inflammasome AIM2 expression.

Conclusions: Overall, we constructed a prognostic model of PCa with six PRLs and identified their expression in PCa cells. The experimental verification showed that AC005253.1 could affect the proliferation, migration, and invasion abilities of PCa cells. Meanwhile, AC005253.1 may play an important role in PCa by affecting pyroptosis through the AIM2 inflammasome. This result requires further research for verification.