<p>Circ_0000885 Enhances Osteosarcoma Progression by Increasing FGFR1 Expression via Sponging MiR-1294</p>

Abstract

Background: As a malignant tumor, the progression of osteosarcoma (OS) is mediated by multiple regulators, including circular RNAs (circRNAs). However, the role of circ_0000885 in OS is unclear. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ_0000885, miR-1294 and fibroblast growth factor receptor 1 (FGFR1). Cell proliferation was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Flow cytometry and transwell assay were employed to determine the cell cycle distribution, cell migration and invasion, respectively. Moreover, the relationship between miR-1294 and circ_0000885 or FGFR1 was confirmed by dual-luciferase reporter assay. The protein level of FGFR1 was assessed via Western blot (WB) analysis. Animal experiments were used to verify the effect of circ_0000885 silencing on OS tumor growth in vivo. Results: Circ_0000885 level was increased in OS tissues and cells. Knockdown of circ_0000885 repressed the proliferation, migration, invasion and induced cell cycle arrest in OS cells. There was a binding relationship between miR-1294 and circ_0000885, and miR-1294 inhibitor could reverse the inhibitory effect of silenced circ_0000885 on OS progression. MiR-1294 could target FGFR1, and overexpressed FGFR1 could invert the suppression effect of miR-1294 mimic on OS progression. Silencing of circ_0000885 hindered FGFR1 expression, while this effect could be recovered by miR-1294 inhibitor. In addition, circ_0000885 knockdown reduced OS tumor growth via regulating the FGFR1 expression by sponging miR-1294 in vivo. Conclusion: Circ_0000885 played an active role in OS progression, indicating that it might be a potential target for OS therapy.

Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis

“…Full-text assessment included 60 articles, and hand search did not identify additional relevant articles. Finally, 52 articles were included in the qualitative analysis [ 31 – 82 ]. Thirty-eight articles on clinicopathology and 36 articles on prognosis were included in the quantitative analysis after the exclusion of articles with incomplete data.…”

Knockdown of hsa_circ_0043691 restrains the progression of gastric cancer by decoying miR‐1294 to target pre‐leukemia transcription factor 3

“…In this work, hsa_circ_0043691 and miR‐1294 were predicted to have binding sites by using circinteractome bioinformatics software, and this relationship was testified by multiple assays. Previous studies have found that miR‐1294 plays an antitumor effect in the malignant phenotype of many of cancer, including esophageal cancer, 29 osteosarcoma, 30 and laryngeal squamous cell carcinoma cell (LSCC) 31 . In GC tissues, downregulated miR‐1294 was uncovered in GC tissue samples and cells 32–34 .…”

The tumor suppressor role and ceRNA network of miR-1294 in cancer

“…The ceRNAs of miR-1294 are highly expressed in 11 tumors, and by inhibiting the expression of miR-1294, they promote the occurrence and development of cancer (Tables 1 and 2). These ceRNAs are 3 lncRNAs and 16 circRNAs, including lncRNA TUG1 [7] in esophageal cancer (EC), KRT16P2 [8] in laryngeal squamous cell carcinoma (LSCC), and NEAT1 [9] in gastric cancer (GC); circRNAs include circ_0023984 in esophageal squamous cancer (ESCC) [10], circ_0005198 [11] and circ_0000936 [12] in glioma (GRAMD1A), and circAMOTL1 in oral squamous cell carcinoma (OSCC) [13], circ_0000885 [14] and circOMA1 [15] in osteosarcoma (OS), circ_0030235 [16] and circEYA3 [17] in pancreatic ductal adenocarcinoma (PDAC), circ_0004370 [18] in EC, circ_0000854 [19], circPRKCI [20], circCAMSAP1 [21], circUBAP2 [22], and circ_0000854 [23] in hepatocellular carcinoma (HCC), circPLK1 in malignant pleural mesothelioma (MPM) [24], circPLK1 [25] and circSHKBP1 [26] in non-small cell lung cancer (NSCLC), and circCDK17 [27], circ_0018289 [28] in cervical cancer (CC). Furthermore, miR-1294 was downregulated in ovarian cancer (OC) and clear cell renal cell carcinoma (ccRCC), thereby relaxing its repressive effects on insulin-like growth factor 1 receptor (IGF1R) and homeobox A6 (HOXA6).…”

“…Aberrant activation of the RAS pathway is a highly prevalent major oncogenic event [46]. Circ_0000885, which is highly expressed in OS, can restore the expression level of FGFR1 by targeting miR-1294, thereby mediating the activation of the RAS signaling pathway and promoting the progression of OS [14].…”