Comprehensive Analysis of a ceRNA Network Identifies lncR-C3orf35 Associated with Poor Prognosis in Osteosarcoma

Abstract

Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

C10orf55, CASC2, and SFTA1P lncRNAs Are Potential Biomarkers to Assess Radiation Therapy Response in Head and Neck Cancers

“…Finally, the C10orf55, C3orf35, C5orf38, CASC2, MEG3, MYCNOS, SFTA1P, SNHG3, and TMEM105 lncRNAs, were validated using HNSCC cell line models, which were irradiated using 2, 4, and 8 Gy of doses and compared to the non-irradiated controls (0 Gy). Changes in the expression were assessed using the 2 −∆Ct method and normalized to the GAPDH reference gene [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”

“…The primers for quantification of C10orf55, C3orf35, C5orf38, CASC2, MEG3, MYCNOS, SFTA1P, SNHG3, and TMEM105 were described previously [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ] and are presented in Table 1 . The compatibility of all primers and their complementarity to the target sequence was checked using the Basic Local Alignment Search Tool (BLAST), National Center for Biotechnology Information (NCBI), Bethesda, Maryland, United States of America, available at: , accessed on 15 May 2022.…”

“…The compatibility of all primers and their complementarity to the target sequence was checked using the Basic Local Alignment Search Tool (BLAST), National Center for Biotechnology Information (NCBI), Bethesda, Maryland, United States of America, available at: , accessed on 15 May 2022. All real-time PCR data were analyzed by calculating the 2 −∆Ct method and normalized against the GAPDH expression as described previously [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Bioinformatics and Experimental Analyses Reveal Immune-Related LncRNA–mRNA Pair AC011483.1-CCR7 as a Biomarker and Therapeutic Target for Ischemic Cardiomyopathy

“…Moreover, one study provided the first evidence that NBR2 is relevant with myocardial hypertrophy by finding that NBR2 inhibits endoplasmic reticulum (ER) stress and myocardial hypertrophy by modulating the LKB1/AMPK/Sirt1 pathway [ 37 ]. C3orf35 , also known as APRG1 , was associated with poor prognosis of osteosarcoma and may affect tumor metastasis and immune cell infiltration in osteosarcoma patients [ 38 ]. AC011483.1 is a lncRNA antisense to KLK6 , KLK7 , KLK8 , and KLK9 genes.…”