miR-133a-3p在胃癌组织和血浆中的表达及其对胃癌细胞增殖的影响

Expression of miR-133a-3p in gastric cancer tissues and plasma and its effect on proliferation of gastric cancer cells

目的:检测mi R-133a-3p在胃癌组织及患者血浆中的表达水平及其对胃癌细胞增殖的影响,并探讨其与患者预后的关系。方法:收集河北医科大学第四医院普外科2012年5月至2013年5月胃癌手术切除的组织标本及术前外周静脉血标本52例,每例组织标本采集肿瘤组织(非坏死部分)和配对的癌旁组织。采用实时荧光定量RT-PCR(RT-q PCR)法检测mi R-133a-3p在胃癌组织、癌旁组织、血浆及健康体检者血浆(35例)的表达情况,分析mi R-133a-3p的表达水平与胃癌患者中位DFS及临床病理特征的关系。CCK-8法检测过表达或沉默mi R-133a-3p对胃癌SGC7901细胞增殖的影响。结果:mi R-133a-3p在胃癌组织中的表达明显降低(P<0.01),其表达水平与肿瘤TNM分期、肿瘤侵润深度(T)、淋巴结转移(N)及脉管瘤栓相关(P<0.01);在胃癌患者血浆中的表达明显升高(P<0.01),其表达水平与肿瘤TNM分期、淋巴结转移(N)及脉管瘤栓相关(P<0.05);与患者血清中CA199的表达水平正相关(P<0.01)。胃癌组织中mi R-133a-3p高表达组患者中位DFS明显高于低表达组(20.8 vs 14.8个月,P<0.05)。血浆中mi R-133a-3p的高表达组患者中位DFS明显低于低表达组(14.4 vs 20.3个月,P<0.05)。过表达mi R-133a-3p可明显抑制SGC7901细胞的增殖能力,同样沉默其表达可明显促进SGC701细胞的增殖能力(均P<0.05)。结论:mi R-133a-3p可明显抑制胃癌细胞SGC7901的增殖能力,在胃癌组织和血浆中存在明显异常表达,其表达与患者预后明显相关,可作为胃癌早诊早治及患者临床预后判定的潜在标志物。

Objective： To detect the expression of mi R-133 a-3 p in gastric cancer（GC） tissues and plasma of GC patients, and to investigate its effect on the proliferation of GC cells as well as its correlation toprognosis of GC patients. Methods： 52 cases of cancertissues（non-necrosis part） and corresponding adjacent tissues as well as the pre-operative peripheral blood samples from GC patients, who underwent surgery at Department of General Surgery, the Forth Hospital of Hebei Medical University（Shijiazhuang, China） between May2012 and May 2013, were collected for this study. The plasma sample（n=35） from healthy donors were obtained during their physical examination. RT-q PCR was adopted to detect the expression of mi R-133 a-3 p in gastric cancer tissues, adjacent tissuesand plasma samples of GC patients and healthy volunteers. The relationships between mi R-133 a-3 p expression and the median DFS as well as clinicopathological parameters were also analyzed. CCK-8 assay was adopted to detect the effect of mi R-133 a-3 p silence or over-expression on proliferation of gastric cancer SGC7901 cells. Results： mi R-133 a-3 p was dramatically decreased in gastric cancer tissues（P〈0.01）,and its expression was associated with TNM stage, tumor infiltration（T）, lynphonode metastasis（N）, and vascular tumor thrombus（all P〈0.01）; mi R-133 a-3 p was significantly increased in the plasma of GC patients（P〈0.01）, and its expression was associated with TNM stage, lynphonode metastasis（N）, and vascular tumor thrombus（all P〈0.05）. mi R-133 a-3 p expression was positively correlated with serum CA199 level of GC patients（P〈0.01）. The median DFS of patients with high mi R-133 a-3 pexpression in cancer tissues was significantly longer than that of the patients with low expression（20.8 vs 14.8 months, P〈0.05）; The median DFS of patients with high plasma mi R-133 a-3 p expression was significantly shorter than that of the patients with low expression（14.4 vs 20.3 months, P〈0.05）. Over-expression of mi R-133 a-3 p could significantly inhibit the proliferation of gastric cancer SGC7901 cells, while mi R-133 a-3 p silence could significantly promote the proliferation（all P〈0.05）. Conclusion： mi R-133 a-3 p could significantlyinhibit the proliferation of SGC7901 cells; mi R-133 a-3 p aberrantlyexpressed in gastric cancer tissues and plasma, and obviously correlated with prognosis of gastric cancer patients, which may be used as a potential clinical bio-maker for early diagnosis and treatment as well as the prognosis prediction of gastric cancer.