Department of Orthopaedics, Shanghai Eighth People's Hospital, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2018 Feb;22(4):921-927. doi: 10.26355/eurrev_201802_14371.
Aberrant expression of long noncoding RNA (lncRNA) is associated with carcinogenesis of various tumors. The aim of current study was to explore the clinical significance and biological function of long non-coding RNA HOST2 (lnc-HOST2) in patients with osteosarcoma.
The expression of lnc-HOST2 was detected by quantitative Real-time PCR (qRT-PCR) in 163 osteosarcoma specimens and matched the normal tissues. The significance of lnc-HOST2 as a prognostic factor as well as its relationship with survival was determined. The effects of lnc-HOST2 expression on the biological behavior of osteosarcoma cells were investigated by MTT and flow cytometry. qRT-PCR and Western blot were used to evaluate the mRNA and protein expression of apoptosis-related factors.
The expression levels of lnc-HOST2 in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissues (p < 0.01). Statistical assay indicated that the expression level of lnc-HOST2 was positively correlated with tumor stage (p = 0.003) and distant metastasis (p = 0.000). Furthermore, Kaplan-Meier analysis suggested that patients with high lnc-HOST2 showed poorer overall survival than those with low lnc-HOST2 (p = 0.000). The univariate and multivariate analysis further revealed that lnc-HOST2 expression was an independent prognostic factor for overall survival. Then, functionally, down-regulation of lnc-HOST2 suppressed proliferation and induced cell apoptosis in osteosarcoma cells. Notably, we confirmed that up-regulation of lnc-HOST2 led to Bcl-2 downregulation and Bax upregulation in osteosarcoma cells.
We provided the first evidence that lnc-HOST2 may serve as a novel prognostic marker in osteosarcoma. Further, targeting lnc-HOST2 may represent an attractive target therapy for osteosarcoma.
长链非编码 RNA（lncRNA）的异常表达与各种肿瘤的发生有关。本研究旨在探讨长链非编码 RNA HOST2（lnc-HOST2）在骨肉瘤患者中的临床意义和生物学功能。
通过定量实时 PCR（qRT-PCR）检测 163 例骨肉瘤标本和相应正常组织中 lnc-HOST2 的表达。确定 lnc-HOST2 作为预后因素的意义及其与生存的关系。通过 MTT 和流式细胞术研究 lnc-HOST2 表达对骨肉瘤细胞生物学行为的影响。qRT-PCR 和 Western blot 用于评估凋亡相关因子的 mRNA 和蛋白表达。
骨肉瘤组织中 lnc-HOST2 的表达水平明显高于相应的非癌骨组织（p < 0.01）。统计学分析表明，lnc-HOST2 的表达水平与肿瘤分期（p = 0.003）和远处转移（p = 0.000）呈正相关。此外，Kaplan-Meier 分析表明，lnc-HOST2 高表达的患者总生存率低于 lnc-HOST2 低表达的患者（p = 0.000）。单因素和多因素分析进一步表明，lnc-HOST2 表达是总生存率的独立预后因素。然后，功能上，下调 lnc-HOST2 抑制骨肉瘤细胞增殖并诱导细胞凋亡。值得注意的是，我们证实上调 lnc-HOST2 导致骨肉瘤细胞中 Bcl-2 下调和 Bax 上调。
我们首次提供证据表明，lnc-HOST2 可能成为骨肉瘤的一种新的预后标志物。此外，靶向 lnc-HOST2 可能代表骨肉瘤有吸引力的靶向治疗。
