Clinical Significance and Therapeutic Potential of Long Non‐Coding RNA H19 in Soft Tissue Sarcoma

BACKGROUND: Long non-coding RNA (lncRNA) H19 plays a pivotal role in the pathogenesis of different human cancers, but its role in soft tissue sarcoma (STS) has not yet been defined. METHODS: We analyzed H19 expression patterns in various cancer cell lines, focusing on sarcoma subtypes. RNA in situ hybridization was performed on a tissue microarray (n = 150) to assess H19 expression in human STS samples. Univariate and multivariate analyses were conducted to evaluate H19's prognostic value. In STS cell lines with high H19 expression, a Gapmer-based knock-down approach was used to study the functional impact of H19 expression. RESULTS: Low H19 expression was associated with poor prognosis in univariate analysis (HR: 0.564; 95% CI: 0.324-0.985; p = 0.044). Multivariate analysis showed advanced patient age (p < 0.001) and large tumor size (p = 0.002) as independent predictors of worse overall survival, irrespective of H19 expression (HR: 0.655; 95% CI: 0.367-1.170; p = 0.153). H19 knockdown in STS cell lines reduced cellular growth and increased pro-apoptotic activity. DISCUSSION: Our findings suggest that H19 might play a role in STS pathogenesis. While its prognostic value requires further investigation, H19-based targeting approaches may warrant evaluation for therapeutic potential in STS.