Circ_0001174 facilitates osteosarcoma cell proliferation, migration, and invasion by targeting the miR-186-5p/MACC1 axis

Abstract

Background Studies of aberrantly expressed circular RNAs (circRNAs) can provide insights into the molecular mechanisms of osteosarcoma (OS). However, the role of circ_0001174 in OS progression remains unknown. This study is aimed to identify differentially expressed circRNAs and messenger RNAs (mRNAs) in patients with OS and to investigate potential regulatory ways of circ_0001174. Methods High-throughput sequencing was performed to screen aberrantly expressed circRNAs and mRNAs between tumor and paracancerous tissues from patients with OS. Several bioinformatics tools were used to analyze the functions and pathways of the differentially expressed genes between the tissues. Cell counting kit-8, cell migration and invasion assays were performed to evaluate the functions of the critical circRNAs. RNA interference experiments, quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to explore the relationship between miR-186-5p and circ_0001174 or metastasis-associated in colon cancer 1 (MACC1). Results Compared with the paracancerous tissues, 109 circRNAs and 1264 mRNAs were differentially expressed in the OS tissues, including 88 circRNAs and 707 mRNAs that were upregulated and 21 circRNAs and 557 mRNAs that were downregulated. The expression of four upregulated and four downregulated circRNAs was validated using RT-qPCR; the results were consistent with the sequencing data, and circ_0001174 was found to be significantly upregulated in 16 pairs of OS tissues and OS cell lines (fold change > 2.0, P value < 0.05). Knockdown of circ_0001174 inhibited the proliferation, migration, and invasion of OS cells. Additionally, circ_0001174 directly and negatively modulated the expression of miR-186-5p and positively regulated the expression of MACC1. Conclusions Abnormally high expression of circ_0001174 may promote the proliferation, migration, and invasion of OS cells through up-regulating MACC1 by sponging miR-186-5p. These results provide insight into therapeutic targets for preventing and treating OS.

Circ_LRP6 facilitates osteosarcoma progression via the miR‐122‐5p/miR‐204‐5p/HMGB1 axis

“…30 Circ_0001174 was highly expression and promoted OS progression. 31 Circ-LRP6, has been shown to serve as an oncogene in different cancers, but its mechanism of action in OS is not completely comprehended. In this study, circ-LRP6 was found to be overexpressed in osteosarcoma tissues and cell lines, and that silencing circ-LRP6 inhibited proliferation, migration, and invasion of osteosarcoma cells.…”

“…For example, circ_LARP4 presented down‐regulation in non‐small cell lung cancer (NSCLC) cell lines, and overexpression of it can hinder the proliferation and migration of NSCLC cells and stimulate cell apoptosis 30 . Circ_0001174 was highly expression and promoted OS progression 31 . Circ‐LRP6, has been shown to serve as an oncogene in different cancers, but its mechanism of action in OS is not completely comprehended.…”

Circ0038632 modulates MiR-186/DNMT3A axis to promote proliferation and metastasis in osteosarcoma

“…lncRNA NEAT1 sponges miR‐186‐5p and promotes the progression of osteosarcoma invasion and EMT ( 16 ). Via miR-186-5p, circ_0001174 promotes osteosarcoma progression ( 17 ). Our results showed that circ0038632 could regulate the expression of miR-186 by sponging it ( Figure 3 ).…”