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长链非编码 RNA RUSC1-AS1 通过调控 miR-340-5p 和 PI3K/AKT 通路促进骨肉瘤进展。

LncRNA RUSC1-AS1 promotes osteosarcoma progression through regulating the miR-340-5p and PI3K/AKT pathway.

机构信息

Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, China.

Department of Gynecology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570102, China.

出版信息

Aging (Albany NY). 2021 May 28;13(16):20116-20130. doi: 10.18632/aging.203047.

Abstract

Dysregulation of long noncoding RNA (lncRNA) is frequently involved in the progression and development of osteosarcoma. LncRNA RUSC1-AS1 is reported to be upregulated and acts as an oncogene in hepatocellular carcinoma, cervical cancer and breast cancer. However, its role in osteosarcoma has not been studied yet. In the present study, we investigated the role of RUSC1-AS1 in osteosarcoma both and . The results showed that the expression of RUSC1-AS1 was significantly upregulated in osteosarcoma cell line U2OS and HOS compared to that in human osteoblast cell line hFOB1.19. Similar results were found in human samples. Silencing RUSC1-AS1 by siRNA significantly inhibited U2OS and HOS cell proliferation and invasion, measured by CCK-8 and transwell assay. Besides, knockdown of RUSC1-AS1 increased cell apoptosis in osteosarcoma cell lines. In addition, RUSC1-AS1 promoted the epithelial-mesenchymal transition (EMT) process of osteosarcoma cells. experiments confirmed that RUSC1-AS1 knockdown had an inhibitory effect on osteosarcoma tumor growth. Mechanically, we showed that RUSC1-AS1 directly binds to and inhibits miR-340-5p and activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrated that RUSC1-AS1 promoted osteosarcoma development both and through sponging to miR-340-5p and activating the PI3K/AKT signaling pathway. Therefore, RUSC1-AS1 becomes a potential therapeutic target for osteosarcoma.

摘要

长链非编码 RNA(lncRNA)的失调经常参与骨肉瘤的进展和发展。据报道,lncRNA RUSC1-AS1 在肝癌、宫颈癌和乳腺癌中上调并作为癌基因发挥作用。然而,其在骨肉瘤中的作用尚未得到研究。在本研究中,我们通过 和 研究了 RUSC1-AS1 在骨肉瘤中的作用。结果表明,与成骨细胞系 hFOB1.19 相比,RUSC1-AS1 在骨肉瘤细胞系 U2OS 和 HOS 中的表达明显上调。在人类样本中也发现了类似的结果。通过 siRNA 沉默 RUSC1-AS1 显著抑制 U2OS 和 HOS 细胞增殖和侵袭,通过 CCK-8 和 Transwell 测定法测量。此外,RUSC1-AS1 敲低增加了骨肉瘤细胞系中的细胞凋亡。此外,RUSC1-AS1 促进骨肉瘤细胞的上皮-间充质转化(EMT)过程。 实验证实,RUSC1-AS1 敲低对骨肉瘤肿瘤生长具有抑制作用。从机制上讲,我们表明 RUSC1-AS1 通过与 miR-340-5p 结合并抑制其活性以及激活 PI3K/AKT 信号通路来促进骨肉瘤的发展。总之,我们的研究表明,RUSC1-AS1 通过海绵吸附 miR-340-5p 并激活 PI3K/AKT 信号通路,促进骨肉瘤的发展。因此,RUSC1-AS1 成为骨肉瘤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d1b/8436931/b5d8bf8d48fd/aging-13-203047-g001.jpg

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