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

Abstract

BackgroundPyroptosis 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.MethodsGene 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.ResultsPrognostic 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.ConclusionsOverall, 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.

A review focusing on the role of pyroptosis in prostate cancer

“…In vitro experiments revealed that silencing AC005253.1 inhibited the proliferation, migration, and invasion of PCa cells. [ 93 ] It is evident that ncRNAs associated with scotomies can offer new avenues for clinicians to develop novel drugs. Overall, the role of ncRNAs in the process of cancer cell pyroptosis is intricate, and further experiments are required to investigate precise interventions in different ncRNA-mediated cell pyroptosis and develop more biomarkers and therapeutic targets (Fig.…”

“…[ 98 ] Yu et al identified AC005253.1, an LncRNA associated with PCa pyroptosis, and reported that the inhibition of AC005253.1 expression suppressed the viability, migration and invasion of PCa cells, significantly increased the expression of AIM2 inflammasome, and promoted the pyroptosis in PCa cells. [ 93 ] In view of the findings above, the induction of pyroptosis in PCa cells can be targeted as a new strategy to inhibit tumor growth.…”

“…Besides, AC005253.1 might play an important role in PCa by affecting pyroptosis through the AIM2 inflammasome. [ 93 ] The absence of comprehensive and individualized treatment options contributes significantly to the elevated mortality rates observed in patients with metastatic PCa. The characterization of pyroptosis as a specific cell death pathway and its related gene expression has shown great potential for predicting the risk of PCa.…”