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

Abstract

Background Circular RNAs (circRNAs), a class of noncoding RNAs (ncRNAs), may modulate gene expression by binding to miRNAs. Additionally, recent studies show that circRNAs participate in some pathological processes. However, there is a large gap in the knowledge about circDOCK1 expression and its biological functions in osteogenic sarcoma (OS). Methods Differentially expressed circRNAs in OS cell lines and tissues were identified by circRNA microarray analysis and quantitative real-time PCR (qRT–PCR). To explore the actions of circDOCK1 in vivo and in vitro, circDOCK1 was knocked down or overexpressed. To assess the binding and regulatory associations among miR-339-3p, circDOCK1 and IGF1R, we performed rescue experiments, RNA immunoprecipitation (RIP), RNA pulldown assays and dual-luciferase assays. Moreover, we performed apoptosis assays to reveal the regulatory effects of the circDOCK1/miR-339-3p/IGF1R axis on cisplatin sensitivity. Results CircDOCK1 expression remained stable in the cytoplasm and was higher in OS tissues and cells than in the corresponding controls. Overexpression of circDOCK1 increased oncogenicity in vivo and malignant transformation in vitro. In the U2OS and MG63 cell lines, circDOCK1 modulated tumor progression by regulating IGF1R through sponging of miR-339-3p. Additionally, in the U2OS/DDP and MG63/DDP cell lines, cisplatin sensitivity was regulated by circDOCK1 via the miR-339-3p/IGF1R axis. Conclusions CircDOCK1 can promote progression and regulate cisplatin sensitivity in OS via the miR-339-3p/IGF1R axis. Thus, the circDOCK1/miR-339-3p/IGF1R axis may be a key mechanism and therapeutic target in OS.

Circular RNA circDOCK1 contributes to osteosarcoma progression by acting as a ceRNA for miR-936 to regulate LEF1

“…Here, our work identified a typical exonic circRNA with a circular structure, circDOCK1, which is derived from the parental gene DOCK1. Coincided with the former report [19] , circDOCK1 content was freakishly upregulated in OS tissues and cell lines. Apart from that, in vitro loss-of-function experiments delineated that circDOCK1 absence might dampen cell proliferation, migration, and invasion of OS cells in vitro .…”

“…Of note, multiple works of the literature underscored that circDOCK1 (circBase ID: has_circ_0020378) was differentially expressed in a variety of human tumors and partook in initiating tumorigenesis [17] , [18] . Lately, it has been proved that the upregulation of circDOCK1 might contribute to OS cell carcinogenesis and chemotherapeutic resistance [19] . Nonetheless, its regulatory mechanism in OS progression remains largely unknown.…”

Silencing circOMA1 Inhibits Osteosarcoma Progression by Sponging miR-1294 to Regulate c-Myc Expression

“…Due to its unique circular structure, cirRNA has attracted increasing attention in recent years ( 14 ). Researchers have used second-generation sequencing and gene chip to screen for differentially expressed circRNAs in various tumours and observed that circRNAs have an essential function in tumour proliferation, metastasis, and drug resistance ( 15 – 18 ). For example, has_circ_0018414 accelerated malignant progression of lung adenocarcinoma via sponging miR-6807-3P ( 19 ).…”

Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential

“…Targeting of IGFs, IGF-1R and its downstream targets by antibodies has also been proposed as a strategy to silence IGF-1R signaling with less resistance. An example is B003-2A, a recently developed IGF-1R anti-idiotypic antibody antagonist, which abrogated the IGF-1R-mediated proliferation of ovarian cancer cells in vivo and in vitro and overcame resistance to cisplatin in ovarian cancer cell lines ( 64 , 74 ).…”