Integrative Analysis and Experimental Validation Indicated That SNHG17 Is a Prognostic Marker in Prostate Cancer and a Modulator of the Tumor Microenvironment via a Competitive Endogenous RNA Regulatory Network

Oxid Med Cell Longev. 2022 Jul 12:2022:1747604. doi: 10.1155/2022/1747604. eCollection 2022.

Abstract

The incidence of prostate cancer (PC) is growing rapidly worldwide, and studies uncovering the molecular mechanisms driving the progression and modulating the immune infiltration and antitumor immunity of PC are urgently needed. The long noncoding RNA SNHG family has been recognized as a prognostic marker in cancers and contributes to the progression of multiple cancers, including PC. In this study, we aimed to clarify the prognostic values and underlying mechanisms of SNHGs in promoting the progression and modulating the tumor microenvironment of PC through data mining based on The Cancer Genome Atlas (TCGA) database. We identified that within the SNHG family, SNHG17 was most correlated with the overall survival of PC patients and could act as an independent predictor. Moreover, we constructed a competitive endogenous RNA (ceRNA) network by which SNHG17 promotes progression and potentially inhibits the immune infiltration and immune response of prostate cancer. By interacting with miR-23a-3p/23b-3p/23c, SNHG17 upregulates the expression of UBE2M and OTUB1, which have been demonstrated to play critical roles in the tumorigenesis of human cancers, more importantly promoting cancer cell immunosuppression and resistance to cytotoxic stimulation. Finally, we examined the correlation between SNHG17 expression and the clinical progression of PC patients based on our cohort of 52 PC patients. We also verified the SNHG17/miR-23a/OTUB1 axis in RV-1 and PC-3 cells by dual luciferase and RIP assays, and we further identified that SNHG17 promoted cellular invasive capacity by modulating OTUB1. In summary, the current study conducted a ceRNA-based SNHG17-UBE2M/OTUB1 axis and indicated that SNHG17 might be a novel prognostic factor associated with the progression, immunosuppression, and cytotoxic resistance of PC.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prognosis
  • Prostatic Neoplasms* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Tumor Microenvironment / genetics
  • Ubiquitin-Conjugating Enzymes / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Ubiquitin-Conjugating Enzymes
  • UBE2M protein, human