Center for Joint Surgery, Southwest Hospital, Third Military Medical University, Chongqing (Army Medical University), China.
Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5857-5866. doi: 10.26355/eurrev_201809_15915.
Osteosarcoma (OS) is the most common primary malignancy, mainly arising from the metaphysic of the long bones of adolescents and young adults. Although osteosarcoma has been studied widely, the underlying molecular mechanism remains unclear. Increasing evidence shows that abnormal long non-coding RNAs (LncRNAs) expression is involved in tumorigenesis. The aim of this study was to identify the detailed role of LncRNA LINC00628 in osteosarcoma.
The relative mRNA expression level of LINC00628 in adjacent tissues, osteosarcoma tissues with or without metastasis and osteosarcoma cell lines were detected by qRT-PCR. Overall survival curves for two groups defined by high and low expression level of LINC00628 in osteosarcoma patients. The cell proliferation, invasion and migration in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were detected. The cell cycle distribution and apoptosis rate in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were measured using the Flow cytometry analysis. The relative protein expression level of p-PI3K, p-Akt, P53 and Bcl-2 in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were detected by Western blot.
LINC00628 expression was significantly decreased in osteosarcoma tissues compared with adjacent tissues. Meanwhile, osteosarcoma tissues with metastasis were significantly associated with a low expression level of LINC00628 and the low expression level of LINC00628 has a lower overall survival rate. LINC00628 expression was increased in osteosarcoma cell lines after transfection with lncRNA-LINC00628 and the cell proliferation, invasion and migration in osteosarcoma cells after transfection with lncRNA-LINC00628 were significantly inhibited. Moreover, the cell cycle was arrested in G0/G1 phase and the apoptosis rate was increased in osteosarcoma cells after transfection with lncRNA-LINC00628. Mechanistically, the relative protein expression level of p-PI3K, p-Akt and Bcl-2 were significantly increased and the relative expression of P53 was significantly decreased in osteosarcoma cells after transfection with lncRNA-LINC00628.
LINC00628 expression was decreased in osteosarcoma. The overexpression of LINC00628 inhibited the proliferation, invasion and migration and promoted cell apoptosis in osteosarcoma cells through the inactivation of PI3K/Akt signaling pathway. This lncRNA may be involved in the development and progression of osteosarcoma.
骨肉瘤（OS）是最常见的原发性恶性肿瘤，主要发生于青少年和年轻成人的长骨干骺端。尽管骨肉瘤已经得到广泛研究，但潜在的分子机制仍不清楚。越来越多的证据表明，异常的长非编码 RNA（LncRNA）表达参与了肿瘤发生。本研究旨在鉴定 LncRNA LINC00628 在骨肉瘤中的详细作用。
采用 qRT-PCR 检测相邻组织、有或无转移的骨肉瘤组织和骨肉瘤细胞系中 LINC00628 的相对 mRNA 表达水平。根据骨肉瘤患者 LINC00628 表达水平的高低，绘制两组的总生存曲线。转染 LncRNA-NC 或 LncRNA-LINC00628 后，检测骨肉瘤细胞的增殖、侵袭和迁移。采用流式细胞术分析转染 LncRNA-NC 或 LncRNA-LINC00628 后骨肉瘤细胞的细胞周期分布和凋亡率。采用 Western blot 检测转染 LncRNA-NC 或 LncRNA-LINC00628 后骨肉瘤细胞中 p-PI3K、p-Akt、P53 和 Bcl-2 的相对蛋白表达水平。
与相邻组织相比，LINC00628 在骨肉瘤组织中的表达明显降低。同时，有转移的骨肉瘤组织与 LINC00628 的低表达显著相关，且 LINC00628 低表达的总生存率较低。转染 LncRNA-LINC00628 后，骨肉瘤细胞系中 LINC00628 的表达增加，转染 LncRNA-LINC00628 后骨肉瘤细胞的增殖、侵袭和迁移明显受到抑制。此外，转染 LncRNA-LINC00628 后骨肉瘤细胞的细胞周期被阻滞在 G0/G1 期，凋亡率增加。机制上，转染 LncRNA-LINC00628 后，骨肉瘤细胞中 p-PI3K、p-Akt 和 Bcl-2 的相对蛋白表达水平明显升高，P53 的相对表达水平明显降低。
LINC00628 在骨肉瘤中表达下调。过表达 LINC00628 通过抑制 PI3K/Akt 信号通路的激活，抑制骨肉瘤细胞的增殖、侵袭和迁移，促进细胞凋亡。这种 LncRNA 可能参与骨肉瘤的发生和发展。
