调控结直肠癌转移相关基因SATB2中重要miRNAs在直肠癌肿瘤进展中作用研究

Role of miRNAs and SATB2 protein in development and metastasis of colorectal cancer

目的研究调控结直肠癌转移相关基因特定富含AT碱基DNA序列结合蛋白2(SATB2)中重要转录后调节分子(miRNAs)在结直肠癌肿瘤侵袭、转移中的作用。方法纳入2011年3月至2015年9月本院72例结直肠癌患者为观察组,其中42例已发生远处转移(转移组),30例为原发性未转移患者(未转移组),另纳入同期60例体检健康者为对照组。采用miRNA原位杂交法和免疫组化法测定各组患者间miR-31、miR-92、miR-182及miR-205表达水平。结果转移组miR-31和miR-182分别为(2.38±0.63)和(1.78±0.23),显著高于未转移组和对照组(P<0.05),miR-92和miR-205分别为(15.5±1.02)和(0.52±0.04),显著低于未转移组和对照组(P<0.05)。三组SATB2表达水平有显著性差异(H=42.769,P=0.05)。miR-31和miR-182检测结果与SATB2表达水平呈显著负相关性(r=-0.9782,-0.9711),miR-92和miR-205检测结果与SATB2表达水平呈显著正相关性(r=0.9369,0.955)。结论 miR-31和miR-182在结直肠癌中负性调控SATB2表达,miR-92和miR-205能促进SATB2表达,影响肿瘤增殖转移过程。

Objective To study the effects of post transcriptional regulatory molecules（miRNAs） in colorectal cancer metastasis associated gene specific AT base DNA binding protein 2（SATB2） in invasion and metastasis of colorectal tumors.Methods Fourty-two patients with colorectal cancer with distant metastasis who were admitted to our hospital from March 2011 to September 2015 were selected as the metastasis group and 30 patients with colorectal cancer without metastasis were selected as non-metastasis group.Sixty healthy subjects were included as the control group.The levels of miR-31,miR-92,miR-182 and miR-205 were measured by miRNA in situ hybridization and immunohistochemistry.The correlation between miRNA,target protein SATB2,and the occurrence,development and metastasis of colorectal cancer were analyzed.Results miR-31 and miR-182 were significantly higher in the metastasis group [（2.38±0.63）,（1.78±0.23）,respectively] than those in the non-metastasis group.miR-92 and miR-205 [（15.5±1.02） and（0.52 ±0.04）,respectively] in the control group were significantly lower（P〈0.05）.The differences in levels of SATB2 among the three groups were marginally significant（H=42.769,P=0.05）.Levels of miR-31 and miR-182 were negatively correlated with level of SATB2（r =-0.9357,-0.9711） and levels of miR-92 and miR-205 were positively correlated with level of SATB2（r =-0.9369,-0.955）.Conclusion miR-31 and miR-182 could negatively regulate the expression of SATB2 in colorectal cancer,while miR-92 and miR-205 could enhance the expression of SATB2.These miRNA could affect the proliferation and metastasis of tumors.