Department of Orthopaedics, The Affiliated Huaian Hospital of Xuzhou Medical University, Huaian, Jiangsu 223002, P.R. China.
Int J Mol Med. 2021 Mar;47(3). doi: 10.3892/ijmm.2021.4859. Epub 2021 Feb 4.
Osteosarcoma (OS) is a musculoskeletal malignancy that originates from interstitial cells. An increasing number of studies have verified that long non‑coding RNAs (lncRNAs) participate in the progression of numerous types of cancer. It has been reported that LINC00467 is a cancer‑promoting gene in some types of cancer; however, the regulatory mechanism of LINC00467 in OS remains unknown. In the present study, reverse transcription-quantitative PCR was used to determine LINC00467 expression in OS tissues and cells. Additionally, the impact of LINC00467‑knockdown on OS cell proliferation, migration and invasion was analyzed using Cell Counting Kit‑8, colony formation and Transwell assays, as well as western blot analysis. RNA pulldown and luciferase reporter assays were conducted to investigate the regulatory mechanism of LINC00467 in OS. The results delineated that LINC00467 expression was elevated in OS tissues and cells, and that high LINC00467 expression was associated with a poor prognosis in patients with OS. LINC00467 inhibition suppressed OS progression by inhibiting cell proliferation, migration, invasion and epithelial‑mesenchymal transition. LINC00467 served as a molecular sponge for microRNA (miR)‑217, while karyopherin subunit α4 (KPNA4) was a downstream target gene of miR‑217. Moreover, the overexpression of KPNA4 reversed the inhibitory effects of LINC00467 inhibition on OS progression. Therefore, the present study elucidated the potential mechanism of LINC00467 in OS and indicated that LINC00467 exerted its carcinogenic effects on OS through the miR‑217/KPNA4 axis, implying that LINC00467 may be a novel potential therapeutic target for OS.
骨肉瘤（OS）是一种起源于间质细胞的肌肉骨骼恶性肿瘤。越来越多的研究证实，长链非编码 RNA（lncRNA）参与了多种类型癌症的进展。据报道，LINC00467 是某些类型癌症中的促癌基因；然而，LINC00467 在 OS 中的调节机制尚不清楚。在本研究中，使用逆转录定量 PCR 测定 OS 组织和细胞中 LINC00467 的表达。此外，通过细胞计数试剂盒-8、集落形成和 Transwell 分析以及 Western blot 分析分析了 LINC00467 敲低对 OS 细胞增殖、迁移和侵袭的影响。进行 RNA 下拉和荧光素酶报告基因分析以研究 LINC00467 在 OS 中的调节机制。结果描绘了 LINC00467 在 OS 组织和细胞中的表达升高，并且 LINC00467 高表达与 OS 患者的预后不良相关。LINC00467 抑制通过抑制细胞增殖、迁移、侵袭和上皮-间充质转化来抑制 OS 进展。LINC00467 作为 microRNA（miR）-217 的分子海绵，而核孔蛋白亚单位α4（KPNA4）是 miR-217 的下游靶基因。此外，KPNA4 的过表达逆转了 LINC00467 抑制对 OS 进展的抑制作用。因此，本研究阐明了 LINC00467 在 OS 中的潜在机制，并表明 LINC00467 通过 miR-217/KPNA4 轴发挥其致癌作用在 OS 中，表明 LINC00467 可能是 OS 的一种新的潜在治疗靶点。
