Liu Qiuliang, Geng Peishuo, Shi Longyan, Wang Qi, Wang Pengliang
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Oncol Lett. 2019 Jan;17(1):883-890. doi: 10.3892/ol.2018.9646. Epub 2018 Oct 31.
Osteosarcoma (OS) is an aggressive malignant neoplasm that arises from primitively transformed cells of mesenchymal origin, and that exhibits osteoblastic differentiation and produces malignant osteoid. MicroRNAs (miRNAs) have been widely reported to have important regulatory roles in various human tumors, including OS. However, the potential mechanism of miR-29 in OS remains largely unknown. miR-29 was highly expressed in OS and overexpression of miR-29 promoted OS cell proliferation, as well as proliferating cell nuclear antigen (PCNA) expression and migration, whereas lower expression of miR-29 inhibited OS cell proliferation, PCNA expression and migration. In the present study, a dual-luciferase reporter system supporting phosphatase and tensin homolog (PTEN) was a target of miR-29 and its expression was inhibited by miR-29 mimic, but increased by miR-29 inhibitor. Overexpression of PTEN inhibited OS cell proliferation and migration and it could attenuate miR-29 promotion effect on OS progression. Overall, the results revealed that miR-29, as a tumor promoter, is involved in OS progression and metastasis by targeting PTEN, indicating that the miR-29/PTEN pathway is a potential therapeutic target for the treatment of OS.
骨肉瘤（OS）是一种侵袭性恶性肿瘤，起源于间充质来源的原始转化细胞，具有成骨细胞分化并产生恶性类骨质。微小RNA（miRNA）已被广泛报道在包括OS在内的各种人类肿瘤中发挥重要调节作用。然而，miR-29在OS中的潜在机制仍 largely unknown。miR-29在OS中高表达，miR-29的过表达促进OS细胞增殖以及增殖细胞核抗原（PCNA）表达和迁移，而miR-29表达降低则抑制OS细胞增殖、PCNA表达和迁移。在本研究中，支持磷酸酶和张力蛋白同源物（PTEN）的双荧光素酶报告系统是miR-29的靶标，其表达受到miR-29模拟物的抑制，但受到miR-29抑制剂的增加。PTEN的过表达抑制OS细胞增殖和迁移，并且可以减弱miR-29对OS进展的促进作用。总体而言，结果表明，miR-29作为肿瘤促进因子，通过靶向PTEN参与OS进展和转移，表明miR-29/PTEN途径是治疗OS的潜在治疗靶点。
