Cao Chenggang, Shu Xiaolei
Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital/Chongqing First People's Hospital, Chongqing 400011, P.R. China.
Department of Radiation Oncology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, P.R. China.
Exp Ther Med. 2021 Oct;22(4):1106. doi: 10.3892/etm.2021.10540. Epub 2021 Aug 3.
Osteosarcoma (OS) is a common type of primary malignant tumor. Although the pathogenesis of OS has been extensively studied, the underlying molecular mechanisms have remained to be fully elucidated. Accumulating evidence has revealed that dysregulation of various circular RNAs (circRNAs) is associated with tumorigenesis and recent studies have indicated that circRNA circ_0008932 is aberrantly expressed in tumors. In the present study, the expression and detailed function of circ_0008932 in OS were elucidated. The levels of circ_0008932 in OS samples and cell lines were examined using reverse transcription-quantitative PCR. A cell model with circ_0008932 knockdown was generated using specific small interfering RNA (si-circ_0008932). Cell viability was determined by a Cell Counting Kit-8 assay, the cell migratory/invasive capacity was evaluated using Transwell assays and cell apoptosis was assessed by flow cytometry. The results suggested that circ_0008932 was upregulated in most primary OS tumors, suggesting that circ_0008932 is associated with the development of OS. In the assays, si-circ_0008932 inhibited the proliferation, migration and invasion of OS cells, while apoptosis was promoted. A luciferase reporter assay revealed that circ_0008932 may downregulate microRNA (miR)-145-5p through direct binding. Furthermore, the expression of miR-145-5p was negatively correlated with circ_0008932 levels in OS specimens. In addition, further functional studies indicated that miR-145-5p inhibitors eliminated the effects caused by si-circ_0008932 in OS cells. In comparison, the changes in the biological behavior of OS cells transfected with si-circ_0008932 were enhanced by miR-145-5p. In summary, circ_0008932 may be a novel oncogenic factor during the progression and development of OS by targeting miR-145-5p; more importantly, circ_0008932 may be a potential therapeutic target for OS.
骨肉瘤(OS)是一种常见的原发性恶性肿瘤。尽管对骨肉瘤的发病机制已进行了广泛研究,但其潜在的分子机制仍有待充分阐明。越来越多的证据表明,各种环状RNA(circRNA)的失调与肿瘤发生有关,最近的研究表明,circRNA circ_0008932在肿瘤中异常表达。在本研究中,阐明了circ_0008932在骨肉瘤中的表达及其详细功能。使用逆转录定量PCR检测骨肉瘤样本和细胞系中circ_0008932的水平。使用特异性小干扰RNA(si-circ_0008932)构建了circ_0008932敲低的细胞模型。通过细胞计数试剂盒-8检测法测定细胞活力,使用Transwell检测法评估细胞迁移/侵袭能力,并通过流式细胞术评估细胞凋亡。结果表明,circ_0008932在大多数原发性骨肉瘤肿瘤中上调,提示circ_0008932与骨肉瘤的发生发展有关。在实验中,si-circ_0008932抑制了骨肉瘤细胞的增殖、迁移和侵袭,同时促进了细胞凋亡。荧光素酶报告基因检测显示,circ_0008932可能通过直接结合下调微小RNA(miR)-145-5p。此外,在骨肉瘤标本中,miR-145-5p的表达与circ_0008932水平呈负相关。此外,进一步的功能研究表明,miR-145-5p抑制剂消除了si-circ_0008932对骨肉瘤细胞的影响。相比之下,miR-145-5p增强了转染si-circ_0008932的骨肉瘤细胞生物学行为的变化。总之,circ_0008932可能通过靶向miR-145-5p成为骨肉瘤进展和发展过程中的一种新型致癌因子;更重要的是,circ_0008932可能是骨肉瘤的一个潜在治疗靶点。