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微小RNA-195对胶质瘤患者预后及人胶质瘤细胞增殖和凋亡的影响

Effects of microRNA-195 on the Prognosis of Glioma Patients and the Proliferation and Apoptosis of Human Glioma Cells.

作者信息

Jia Ying, Tian Ye, An Shuo, Yang Dong

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Department of Otorhinolaryngology, Tianjin Medical University General Hospital, No.154 An Shan Dao, Heping District, Tianjin, 300052, China.

出版信息

Pathol Oncol Res. 2020 Apr;26(2):753-763. doi: 10.1007/s12253-019-00622-3. Epub 2019 Feb 26.

Abstract

Glioma is the most common and aggressive intracranial malignant tumor with poor prognosis. Acts as a tumor suppressor, microRNA-195 (miR-195) plays important roles in a variety of cancers. However, the expression of miR-195 and role of miR-195 in glioma are still not well understood. 186 patients with glioma were enrolled and the follow-up period ranges from 1 to 69 months. MiR-195 was exogenously transfected into human glioma U87 cell line. The cell proliferation assay (CCK-8), colony formation assay, cell cycle analysis and cell apoptosis analysis were examined to investigate miR-195 effect on U87 cells. MiR-195 levels were reversely correlated with pathological grades (r = -0.487, p = 0.003). For patients with low miR-195 levels, their median survival time was 15 months, whereas the median survival time in patients with high miR-195 levels was 56.53 months. Multi-factor Cox regression analysis showed that high level of miR-195 (Odds ratio (OR): 0.347, 95% CI: 0.121-0.992) was associated with decreased mortality risk of patients. Moreover, overexpression of miR-195 inhibits proliferation and colony formation, and induces apoptosis of U87 cells. MiR-195 could block the glioma cells in G0/G1 phase, reducing S phase cells and regulating apoptosis related proteins (Caspase-3, Caspase-8, Caspase-9 and Bcl-2). Downregulation of miR-195 was associated with poor prognosis in human glioma. MiR-195 acted as tumor suppressor through inhibiting cell proliferation and promoting cell apoptosis via blockade of cell cycle and regulation of apoptosis related proteins.

摘要

胶质瘤是最常见且侵袭性最强的颅内恶性肿瘤,预后较差。微小RNA-195(miR-195)作为一种肿瘤抑制因子,在多种癌症中发挥重要作用。然而,miR-195在胶质瘤中的表达及作用仍未完全明确。本研究纳入了186例胶质瘤患者,随访时间为1至69个月。将miR-195外源性转染到人胶质瘤U87细胞系中。通过细胞增殖实验(CCK-8)、集落形成实验、细胞周期分析和细胞凋亡分析来研究miR-195对U87细胞的影响。miR-195水平与病理分级呈负相关(r = -0.487,p = 0.003)。miR-195水平低的患者,其生存中位数为15个月,而miR-195水平高的患者生存中位数为56.53个月。多因素Cox回归分析显示,miR-195高水平(比值比(OR):0.347,95%可信区间:0.121 - 0.992)与患者死亡风险降低相关。此外,miR-195过表达抑制U87细胞的增殖和集落形成,并诱导其凋亡。miR-195可使胶质瘤细胞阻滞于G0/G1期,减少S期细胞,并调节凋亡相关蛋白(Caspase-3、Caspase-8、Caspase-9和Bcl-2)。miR-195下调与人胶质瘤预后不良相关。miR-195通过抑制细胞增殖、促进细胞凋亡,经阻滞细胞周期和调节凋亡相关蛋白而发挥肿瘤抑制作用。

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