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Tumor Discovery LncRNA HA117 in osteosarcoma regulation

enriched in 24 GO terms (P < 0.05). All enriched terms in 3.7. Kaplan–Meier survival analysis for 11 key target
each of the three main GO terms are depicted in Figure 3B, genes of HA117
with the most enriched GO terms being blastocyst To elucidate the impact of HA117 target genes on the
development, focal adhesion, and extracellular exosome survival of osteosarcoma patients, we conducted a Kaplan–
(Table S6). Meier overall survival analysis on sarcoma patients,
3.6. Reactome pathway enrichment analysis of focusing on 11 DEGs identified as targets of HA117
HA117 target genes (Table S8). Interestingly, all these 11 genes were down-
regulated after chemotherapy in FFPE samples. Due to the
To assess the biological pathways of HA117 target genes, we significant down-regulation of these genes, we set HR >1
performed pathway enrichment analysis using the Reactome and P < 0.05 as the screening criteria. Although five genes
database. In total, 94 target genes were annotated into 21 had P < 0.05, only BCL7A, NISCH, and PGD met our
Reactome pathway terms (Figure 4 and Table S7). After screening criteria, as the HRs of CHRM2 and NQO1 were
adjusting the P = 0.05, four important pathway terms showed >1. The analysis showed that BCL7A, NISCH, and PGD were
significant enrichment: Interferon-alpha/beta signaling, significantly related to the prognostic of sarcoma (Table S7
cellular responses to stress, cellular responses to stimuli, and and Figure 5). This result indicates that sarcoma patients
cellular response to starvation (Table S7). Among the four with low expression of these three genes had a better overall
pathways, three were related to cell stimulation, and one survival rate, suggesting that low expression of these HA117
was related to signal transduction. In addition, compared target genes may be associated with prolonged survival in
to other pathways, there were significantly more annotated patients. It should be noted that according to our analysis
genes in two pathways: metabolism and immune system, results, HA117 has a positive regulatory relationship with
which had 16 and 15 annotated genes, respectively. The vast BCL7A, indicating that when the expression of HA117
majority of these genes come from HA117-related target decreases, the expression of BCL7A also decreases, which is
genes after chemotherapy, such as NQO1, RPS9, HSPH1, beneficial for patient survival. However, HA117 exhibits a
RPLP1, RPL13, DNAJB9, HIGD1A, PGD, and MTOR. negative regulatory relationship with NISCH and PGD. This
This finding suggests that chemotherapy has a significant finding suggests that, aside from the direct regulatory effects
impact on HA117 target genes, and these genes can serve as of HA117, there may be additional factors influencing the
potential targets for the treatment of osteosarcoma. expression of these two genes. Further research is warranted

Figure 4. Reactome enrichment analysis of HA117 target gene sets. The ordinate represents a Reactome pathway term, while the abscissa represents the
enrichment factor. The size of the bubble represents the number of enrichment genes, and the color of the bubble represents the P-value. Lighter colors
indicate smaller P-values and more significant enrichment.

Volume 3 Issue 3 (2024) 8 doi: 10.36922/td.3670