RESUMO
BACKGROUND: The expression of brain cytoplasmic RNA1 (BCYRN1) is linked to the clinicopathology and prognosis of several types of cancers, among which hepatocellular carcinoma (HCC) is one of the most frequent types of cancer worldwide. AIM: To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis. METHODS: Information was obtained from the Cancer Genome Atlas database. First, the correlation between BCYRN1 expression and prognosis and clinicopathologic characteristics of HCC patients was explored. Univariate and multivariate regression analyses were employed to examine the relationship between BCYRN1 and HCC prognosis. Secondly, potential functions and pathways were explored by means of enrichment analysis of differentially-expressed genes. The relationships between BCYRN1 expression and tumor microenvironment, immune cell infiltration, immune checkpoint, drug sensitivity and immunotherapy effect were also investigated. Finally, three major databases were searched and used to conduct a meta-analysis on the relationship between BCYRN1 expression and patient prognosis. RESULTS: BCYRN1 expression was significantly higher in HCC compared to normal tissues and was linked to a poor prognosis and clinicopathological characteristics. Enrichment analysis showed that BCYRN1 regulates the extracellular matrix and transmission of signaling molecules, participates in the metabolism of nutrients, such as proteins, and participates in tumor-related pathways. BCYRN1 expression was linked to the tumor microenvironment, immune cell infiltration, drug sensitivity and the efficacy of immunotherapy. Furthermore, the meta-analysis in this study showed that BCYRN1 overexpression was related to a worse outcome in HCC patients. CONCLUSION: Overexpression of BCYRN1 relates to poor prognosis and may be a potential prognostic factor and immunotherapeutic target in HCC.
RESUMO
Chemotherapy serves as the first choice in clinic to treat advanced gastric cancer. However, emerging evidence indicated the induction of drug resistance and cancer stem cells occasionally by chemotherapy, which seriously limit the therapeutic effects, but the regulatory mechanism remains unclear. Here we treated two human gastric cancer cell lines SGC7901 and BGC823 with 5-Fluorouracil (5-Fu) or Cisplatin (DDP) in vitro. The survived cells showed significant increase of drug resistance, cell stemness and cytokine GM-CSF expression and secretion. As such, GM-CSF was applied to stimulate gastric cancer cells, followed by the subpopulation of CD133 + CSC analysis, sphere formation assay and stemness genes expression analysis. As a result, CSCs showed induction by GM-CSF treatment. A gastric cancer animal model further indicated that the gastric cancer cells significantly promoted tumor growth after GM-CSF treatment in vivo. High-throughput miRNA and mRNA sequencing analyses identified a subset of miRNAs and mRNAs under regulation of both 5-Fu and GM-CSF in gastric cancer cells, including upregulation of miR-877-3p and downregulation of SOCS2. Targeted overexpression or knockdown of miR-877-3p in gastric cancer cells revealed the oncogenic function of miR-877-3p in regulating gastric cancer by suppressing target gene SOCS2. Jak2/Stat3 signaling pathway, as a downstream target of SOCS2, showed activation in vitro and in vivo after treatment with miR-877-3p or GM-CSF. Our findings not only revealed a novel mechanism through which chemotherapy induced CSCs in gastric cancer via GM-CSF-miRNA-Jak2/Stat3 signaling, but also provided an experimental evidence for appropriate dose reduction of adjuvant chemotherapy in treatment of cancer patients.