Clinical Significance and Therapeutic Potential of Long Non-Coding RNA H19 in Soft Tissue Sarcoma.
Stephan Jahn, Katarina Krajina, Maria Anna Smolle, Dimyana Neufeldt, Katharina Jonas, Beate Rinner, Kevin Mellert, Maxim Noeparast, Martin Trepel, Joanna Szkandera, Martin Pichler, Bernadette Liegl-Azwanger
Abstract
Open AccessBACKGROUND: 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.