bims-myxlip Biomed News
on Myxoid liposarcoma
Issue of 2022–10–02
two papers selected by
Laura Mannarino, Humanitas Research
  1. Transcriptome analysis identifies TODL as a novel lncRNA associated with proliferation, differentiation, and tumorigenesis in liposarcoma through FOXM1 Running Title: TODL lncRNA as a potential therapeutic target for liposarcoma.
  2. Regorafenib for the Treatment of Sarcoma.
  1. Pharmacol Res. 2022 Sep 24. pii: S1043-6618(22)00408-X. [Epub ahead of print] 106462
    Transcriptome analysis identifies TODL as a novel lncRNA associated with proliferation, differentiation, and tumorigenesis in liposarcoma through FOXM1 Running Title: TODL lncRNA as a potential therapeutic target for liposarcoma.
    Deepika Kanojia, Anuradha Kirtonia, Namburi Sai Valli Srujana, Sree Priyanka Jeevanandan, Pavithra Shyamsunder, Shruthi Sanjitha Sampath, Pushkar Dakle, Anand Mayakonda, Harvinder Kaur, Jiang Yanyi, H Phillip Koeffler, Manoj Garg.
      Liposarcoma, the most common soft tissue sarcoma, is a group of fat cell mesenchymal tumors with different histological subtypes. The dysregulation of long non-coding RNAs (lncRNAs) has been observed in human cancers including a few studies in sarcoma. However, the global transcriptome analysis and potential role of lncRNAs remain unexplored in liposarcoma. The present investigation uncovers the transcriptomic profile of liposarcoma by RNA sequencing to gain insight into the global transcriptional changes in liposarcoma. Our RNA sequencing analysis has identified that many oncogenic lncRNAs are differentially expressed in different subtypes of liposarcoma including MALAT1, PVT1, SNHG15, LINC00152, and MIR210HG. Importantly, we identified a highly overexpressed, unannotated, and novel lncRNA in dedifferentiated liposarcomas. We have named it TODL, transcript overexpressed in dedifferentiated liposarcoma. TODL lncRNA displayed significantly higher expression in dedifferentiated liposarcoma cell lines and patient samples. Interestingly, functional studies revealed that TODL lncRNA has an oncogenic function in liposarcoma cells by regulating proliferation, cell cycle, apoptosis, differentiation, and tumorigenesis in the murine model. Silencing of TODL lncRNA highlighted the enrichment of several key oncogenic signaling pathways including cell cycle, transcriptional misregulation, FOXM1 network, p53 signaling, PLK1 signaling, FoxO, and signaling Aurora signaling pathways. RNA pull-down assay revealed the binding of TODL lncRNA with FOXM1, an oncogenic transcription factor, and the key regulator of the cell cycle. Silencing of TODL lncRNA also induces adipogenesis in dedifferentiated liposarcomas. Altogether, our finding indicates that TODL could be utilized as a novel, specific diagnostic biomarker, and a pharmacological target for therapeutic development in controlling aggressive and metastatic dedifferentiated liposarcomas.
    Keywords:  Adipogenesis; Cell cycle; Differentiation; FOXM1; Liposarcoma; TODL long non-coding RNA
    DOI:  https://doi.org/10.1016/j.phrs.2022.106462
  2. Curr Treat Options Oncol. 2022 Sep 30.
    Regorafenib for the Treatment of Sarcoma.
    Jean-Yves Blay, Florence Duffaud, Suzanne George, Robert G Maki, Nicolas Penel.
       OPINION STATEMENT: Sarcomas are a rare group of tumors with many subtypes, conventionally classified into soft-tissue sarcomas and bone sarcomas. Chemotherapeutic regimens form the mainstay of systemic therapy but are not well defined beyond the first-line setting and clinical outcomes are variable. Tyrosine kinase inhibitors (TKIs), with a broad inhibition profile which have been shown to target tumor angiogenesis, have an established role in the treatment of sarcomas without characteristic driver alterations. One such TKI, regorafenib, has been evaluated in sarcomas and clinical data are discussed in this review. An overview of regorafenib data from five phase 2 and one phase 1b clinical trials in over 10 sarcoma subtypes (both soft-tissue and bone) in adult and pediatric patients is reviewed. Regorafenib demonstrated clinical benefit in patients with non-adipocytic soft-tissue sarcomas, osteosarcoma and Ewing sarcoma who had progressed on prior therapy. Patients with otherwise limited treatment options may therefore benefit from regorafenib therapy.
    Keywords:  Bone sarcoma; Non-adipocytic sarcoma; Regorafenib; Soft-tissue sarcoma; Tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1007/s11864-022-00990-0
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