Predicting prognosis and immune status in sarcomas by identifying necroptosis-related lncRNAs

Aging (Albany NY). 2024 Jan 8;16(1):493-517. doi: 10.18632/aging.205383. Epub 2024 Jan 8.

Abstract

Background: Sarcomas are a type of highly heterogeneous malignant tumors originating from mesenchymal tissues. Necroptosis is intricately connected to the oncogenesis and progression of tumors. The main goal of this research is to assess the prognostic value of necroptosis-related lncRNAs (NRlncRNAs) in sarcomas and to develop a risk model based on NRlncRNAs to evaluate prognostic and immune status of the sarcomas.

Methods: We screened NRlncRNAs using the gene co-expression network, developed a prognostic risk model of sarcomas, and then verified the model. Following that, various bioinformatics analysis algorithms were employed to analyze the distinct characteristics of patients of the risk model. Furthermore, the function and regulatory mechanism of NRlncRNA SNHG6 in sarcomas were investigated through osteosarcoma cell experiments, such as qRT-PCR, Western blot, CCK-8, clone formation, and transwell assay.

Results: We successfully developed a NRlncRNAs-related prognostic risk model and screened 5 prognosis-related NRlncRNAs, with SNGH6 being the most significant for prognosis of patients. According to results, the significant differences exist in prognosis, clinical characteristics, and tumor immune status among patients of the risk model. The experiments of osteosarcoma cells demonstrated that NRlncRNA SNHG6 knockdown significantly attenuated the cells' proliferation, migration, and invasion. qRT-PCR and WB results showed that SNHG6 regulated AXL and AKT signaling.

Conclusions: We have developed an innovative investigation on NRlncRNAs, which can serve as a reference for diagnosis, therapy, and prognosis of sarcomas. Additionally, we demonstrated that NRlncRNA SNHG6 regulated AXL and AKT signaling in osteosarcoma cells and the proliferation, migration, and invasion of tumor cells.

Keywords: SNHG6; TME; necroptosis; risk model; sarcomas.

MeSH terms

  • Bone Neoplasms* / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Necroptosis / genetics
  • Osteosarcoma* / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt