长链非编码核糖核酸牛磺酸上调基因1在乳腺癌中的表达及其对细胞增殖凋亡的影响

Expression of long noncoding RNA TUG1 and its role in cell proliferation and apoptosis of breast cancer

摘要:

目的  探讨长链非编码核糖核酸（lncRNA）牛磺酸上调基因1（TUG1）在乳腺浸润性导管癌（IDC）中的表达及其对乳腺癌细胞增殖及凋亡功能的影响。方法  筛选2013年1月~12月该院乳腺病科行手术切除并经病理检查证实为IDC患者的乳腺癌及对应癌旁组织40例。运用荧光定量PCR（qRT-PCR）技术检测lncRNA-TUG1在IDC患者肿瘤及癌旁组织中的表达水平，整理分析lncRNA-TUG1表达与患者临床病例资料间的相关性；采用lncRNA-TUG1特异性siRNA转染人乳腺癌MCF-7细胞，采用CCK-8试验检测转染siRNA后MCF-7细胞增殖能力的变化；流式细胞仪检测转染后MCF-7细胞凋亡变化。采用qRT-PCR、Western-blot检测转染后P27表达变化。结果  lncRNA-TUG1在IDC组织中表达水平显著高于对应癌旁组织（t =4.273，P <0.001），IDC组织中lncRNA-TUG1高表达与肿瘤直径增大（P =0.033）及高TNM分期（P = 0.045）显著相关；lncRNA-TUG1特异性siRNA转染MCF-7细胞后可显著抑制细胞增殖（P =0.041）并上调凋亡细胞比例（t =3.206，P =0.007）；qRT-PCR及Western-blot结果证实，沉默lncRNA-TUG1后可显著促进P27 mRNA及蛋白表达水平（P <0.001）。结论  lncRNA-TUG1在IDC组织中表达上调并与肿瘤恶性临床病理特征有关，lncRNA-TUG1可能通过下调抑癌基因P27的表达来促进IDC生长。

Abstract:

Objective To study the expression of long noncoding RNA TUG1 (lncRNA-TUG1) in invasive ductal carcinoma (IDC) and its role in regulating cell proliferation and apoptosis. Methods Fourty IDC and matched tumor adjacent tissues were collected between January and December in 2013. The expression of lncRNA-TUG1 tissues were detected by qRT-PCR. The relationship between lncRNA-TUG1 and clinical features was analyzed by student-t test. lncRNA-TUG1 siRNA was transfected into MCF-7 cells. CCK-8 assay and flow cytometry (FCM) were used to measure cell proliferation and apoptosis, respectively. The expression of P27 in transformed cells was detected by qRT-PCR and Western blot. Results The expression of lncRNA-TUG1 was significantly higher in IDC tissues than in tumor adjacent tissues (P < 0.001). High expression of lncRNA-TUG1 was positively associated with large tumor diameter (P = 0.033) and advanced TNM stage (P = 0.045). Knockdown of lncRNA-TUG1 significantly suppressed cell proliferation and induced apoptosis in MCF-7 cells (P < 0.05). P27 expression was upregulated when lncRNA-TUG1 was silenced (P < 0.05). Conclusions lncRNA-TUG1 is overexpressed in IDC tissues and associated with cell growth. lncRNA-TUG1 may promote IDC progression by inhibiting P27 expression.