Sarcoma Biology Laboratory, Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, 02114.
J Orthop Res. 2014 May;32(5):695-701. doi: 10.1002/jor.22589. Epub 2014 Feb 5.
Reliable prognostic biomarkers for chordoma have not yet been established. Recent studies revealed that expression of miRNA-1 (miR-1) is frequently downregulated in several cancer types including chordoma. The goal of this follow-up study is to investigate the expression of miR-1 as a prognostic biomarker and further confirm the functional role of miR-1 in chordoma cell growth and proliferation. We determined the relative expression levels of miR-1 and Met in chordoma tissue samples and correlated those to clinical variables. The results showed that miR-1 was downregulated in 93.7% of chordoma tissues and expression was inversely correlated with Met expression. miR-1 expression levels also correlated with clinical prognosis. To characterize and confirm the functional role of miR-1 in the growth and proliferation of chordoma cells, miR-1 precursors were stably transfected into chordoma cell lines UCH-1 and CH-22. Cell Proliferation Assay and MTT were used to evaluate cell growth and proliferation. Restoring expression of miR-1 precursor decreased cell growth and proliferation in UCH-1 and CH-22 cells. These results indicate that suppressed miR-1 expression in chordoma may in part be a driver for tumor growth, and that miR-1 has potential to serve as prognostic biomarker and therapeutic target for chordoma patients.
可靠的软骨肉瘤预后生物标志物尚未建立。最近的研究表明，miRNA-1（miR-1）的表达在包括软骨肉瘤在内的几种癌症类型中经常下调。本后续研究的目的是研究 miR-1 作为预后生物标志物的表达，并进一步证实 miR-1 在软骨肉瘤细胞生长和增殖中的功能作用。我们确定了 miR-1 和 Met 在软骨肉瘤组织样本中的相对表达水平，并将其与临床变量相关联。结果表明，miR-1 在 93.7%的软骨肉瘤组织中下调，表达与 Met 表达呈负相关。miR-1 表达水平也与临床预后相关。为了表征和证实 miR-1 在软骨肉瘤细胞生长和增殖中的功能作用，将 miR-1 前体稳定转染到软骨肉瘤细胞系 UCH-1 和 CH-22 中。细胞增殖测定和 MTT 用于评估细胞生长和增殖。恢复 miR-1 前体的表达降低了 UCH-1 和 CH-22 细胞的生长和增殖。这些结果表明，软骨肉瘤中 miR-1 表达的抑制可能部分是肿瘤生长的驱动因素，并且 miR-1 有可能作为软骨肉瘤患者的预后生物标志物和治疗靶点。
