Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression Through the miR-411-5p/RAB9A Signaling Pathway

Abstract

Recently, various studies have identified circular RNAs (circRNAs) to play a significant role in tumorigenesis, thereby showing potential as novel tumor biomarkers. circSIPA1L1 is a newly discoveredcircular RNA, which is formed by back-splicing of SIPA1L1 and is found increased in osteosarcoma (OS). Nevertheless, the specific functions of circSIPA1L1 in OS remain unknown. In the present study, circSIPA1L1 was obtained from a previously reported circRNA microarray in the GEO database (GSE96964). Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA level of circSIPA1L1 in OS cell lines and tissue samples. Bioinformatics analysis, luciferase reporter assays, real-time PCR, RNA pull-down assays and RNA immunoprecipitation (RIP) were employed to verify the binding of circSIPA1L1 with miR-411-5p. Xenograft tumor models were established to identify the role of circSIPA1L1 in vivo. A series of in vitro experiments, such as western blotting, colony formation, transwell assays and anoikis assay were employed to confirm the relationship across circSIPA1L1, miR-411-5p, and RAB9A. Our study confirmed circSIPA1L1 to be upregulated in both human OS samples and OS cell lines. Mechanistically, circSIPA1L1 could serve as a miR-411-5p molecular sponge to increase RAB9A expression, which was confirmed to be a tumor promoter mediating carcinogenesis. Silencing of circSIPA1L1 attenuated the vitality, invasion, migration and proliferation of OS cell lines both in vivo and in vitro. miR-411-5p inhibition or RAB9A overexpression reversed the anti-tumor effects caused by circSIPA1L1 knockdown. Briefly, circSIPA1L1 could function as a driver gene in OS and initiate OS tumorigenesis through the miR-411-5p/RAB9A signaling pathway, which might become a potential therapeutic biomarker for OS treatment.

CircDOCK1 promotes the tumorigenesis and cisplatin resistance of osteogenic sarcoma via the miR-339-3p/IGF1R axis

“…As a result of their distinct characteristics, including their unique structure, cell type-specific and tissue-specific expression, conservation across species, and stable expression in exosomes, blood and saliva [ 31 – 35 ], more than 10,000 different circRNAs have been discovered and researched in various organisms, which has also increased research focus on circRNAs in malignancy [ 28 , 35 – 37 ]. At present, the differential expression of circRNAs in OS tissues has been identified in many studies [ 2 , 19 , 38 ]. Our bioinformatics analysis and experimental verification showed high expression of circDOCK1 in OS tissues and cell lines, suggesting that circDOCK1 may be a regulator of OS progression.…”

“…Studies have revealed that circRNAs are involved in the pathogenesis of multiple cancers [ 13 ], such as breast cancer [ 14 ], cholangiocarcinoma [ 15 ], and glioblastoma [ 16 ]. However, only preliminary studies on the role of circRNAs in OS have been performed [ 17 – 19 ], and a large knowledge gap exists regarding the overall pathophysiological functions of circRNAs in OS.…”

CircMCTP2 (has-circ-0000658) facilitates the proliferation and metastasis of bladder carcinoma through modulating the miR-498/murine double minute-2 axis

“…CircRNAs serve as a sponge of miRNAs to regulate the expression of genes, resulting in the progression of cancers [ 49 ]. To found the targets of circMCTP2, we first mined the GEO database and found 24 miRNAs (18 down-regulated and 6 up-regulated) that were differentially expressed in BC tissues ( n = 3) relative to adjacent noncancerous specimens ( n = 3) ( Figure 4a ).…”

LncRNA ZFAS1 contributes to osteosarcoma progression via miR-520b and miR-520e-mediated inhibition of RHOC signaling

“…Osteosarcoma, also known as osteogenic sarcoma, is verified as the most prevalent type of malignant bone tumor, frequently occurring in adolescents or children under the age of 20. 1 , 2 Osteosarcoma (OS) is the most malignant primary bone tumor originating from primary osteoblasts, which is characterized by the production of osteoid substances. 3 Clinically, osteosarcoma is pathologically characterized by lower limb pain, lumps, anemia, and even toddle.…”