Department of Joint Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 10030, P.R. China.
Department of Joint Surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 10030, P.R. China.
Int J Mol Med. 2021 Feb;47(2):583-594. doi: 10.3892/ijmm.2020.4825. Epub 2020 Dec 18.
Osteosarcoma (OS) is one of the most aggressive malignancies, accompanied by an elevated incidence and a decreased rate of healing. Recently, several long non‑coding RNAs (lncRNAs) have been reported to be involved in OS progression. Although tumor suppressor candidate 7 (TUSC7) was reported as a novel lncRNA, little is known about its biological functions in OS. The present study was designed to explore whether TUSC7 was involved in the pathological development of OS using various methods, including hematoxylin and eosin staining, Cell Counting Kit‑8 assay, colony formation assay and Transwell assay. The present study revealed that TUSC7 expression was downregulated in OS tissues and cell lines compared with in normal tissues and cell lines. Functionally, the current results revealed that overexpression of TUSC7 inhibited OS cell proliferation, migration and invasion, while promoting apoptosis in vitro and in vivo. Next, the subcellular distribution of TUSC7 was examined by nuclear/cytoplasmic RNA fractionation and reverse transcription‑quantitative PCR. Mechanistic studies revealed that TUSC7 exerted its role by sponging microRNA (miR)‑181a in OS cell lines. Ras association domain family member 6 (RASSF6) was confirmed as a target gene of miR‑181a, and the expression levels of RASSF6 were negatively regulated by miR‑181a. Additionally, the results of rescue experiments suggested that overexpression of miR‑181a neutralized the inhibitory effects of TUSC7 overexpression on OS cells. Overall, the present study demonstrated that the tumor suppressor role of TUSC7 in OS progression was mediated through the miR‑181a/RASSF6 axis, which may represent a new therapeutic target for OS.
骨肉瘤(OS)是一种侵袭性很强的恶性肿瘤,其发病率高,愈合率低。最近,有报道称几种长链非编码 RNA(lncRNA)参与了 OS 的进展。尽管肿瘤抑制候选基因 7(TUSC7)被报道为一种新型 lncRNA,但对其在 OS 中的生物学功能知之甚少。本研究旨在通过各种方法,包括苏木精和伊红染色、细胞计数试剂盒-8 检测、集落形成检测和 Transwell 检测,探讨 TUSC7 是否参与 OS 的病理发展。本研究结果显示,与正常组织和细胞系相比,TUSC7 在 OS 组织和细胞系中的表达下调。功能上,本研究结果显示,TUSC7 的过表达抑制了 OS 细胞的增殖、迁移和侵袭,同时促进了体外和体内的细胞凋亡。接下来,通过核/细胞质 RNA 分离和逆转录-定量 PCR 检测 TUSC7 的亚细胞分布。机制研究表明,TUSC7 通过在 OS 细胞系中海绵吸附 microRNA(miR)-181a 发挥其作用。Ras 相关结构域家族成员 6(RASSF6)被确认为 miR-181a 的靶基因,RASSF6 的表达水平受 miR-181a 的负调控。此外,挽救实验的结果表明,miR-181a 的过表达可中和 TUSC7 过表达对 OS 细胞的抑制作用。综上所述,本研究表明,TUSC7 在 OS 进展中的肿瘤抑制作用是通过 miR-181a/RASSF6 轴介导的,这可能代表了 OS 的一个新的治疗靶点。