长链非编码RNA PWRN1通过PI3K/Akt信号通路对乳腺癌细胞增殖、迁移和侵袭的影响  

Effects of long chain non-coding RNA PWRN1 on proliferation,migration and invasion of breast cancer cells via PI3K/Akt signaling

作　　者：程晓磊 王宗站 朱伟 孙折玉 CHENG Xiaolei;WANG Zongzhan;ZHU Wei;SUN Zheyu(Department of Radiotherapy,Qingdao Central Hospital,Qingdao 266042,China)

机构地区：[1]青岛市中心医院放疗二科,山东青岛266042 [2]青岛市中心医院放疗一科,266042 [3]青岛市中心医院肿瘤科,266042

出　　处：《临床肿瘤学杂志》2022年第8期701-707,共7页Chinese Clinical Oncology

摘　　要：目的探讨长链非编码RNA Prader-Willi区域非蛋白质编码RNA 1(PWRN1)是否通过磷脂酰肌醇-3-激酶/丝氨酸苏氨酸蛋白激酶(PI3K/Akt)通路调控乳腺癌细胞增殖、侵袭和迁移过程。方法采用实时荧光定量PCR(qPCR)检测正常乳腺上皮细胞MCF-10A和乳腺癌细胞(BT474、BT549、T47D、MCF7、MDA-MB-453、MDA-MB-231)的PWRN1水平。选择MDA-MB-231细胞并分为空白对照组(不进行转染)、阴性对照组(转染空载体pcDNA3.1)和PWRN1过表达组(转染过表达载体pcDNA3.1-PWRN1)。细胞计数法(CCK-8)、划痕愈合实验和Transwell小室实验分别检测细胞增殖、迁移和侵袭能力。Western blotting和qPCR检测Snail、基质金属蛋白酶9(MMP-9)、磷酸化磷脂酰肌醇3-激酶(p-PI3K)和磷酸化丝氨酸苏氨酸蛋白激酶1(p-Akt1)的水平。结果乳腺癌细胞的PWRN1水平均低于MCF-10A细胞,差异有统计学意义(P<0.05)。与空白对照组和阴性对照组相比,PWRN1过表达组MDA-MB-231细胞的增殖活力(48 h和72 h)减弱、划痕愈合率和穿膜细胞数较少,且Snail、MMP-9、p-Akt1和p-PI3K水平降低,上述差异均有统计学意义(P<0.05)。空白对照组和阴性对照组上述指标的差异无统计学意义(P>0.05)。结论PWRN1可能通过减弱PI3K/Akt信号通路活化来抑制乳腺癌细胞的增殖、侵袭和迁移,PWRN1/PI3K/Akt轴有作为乳腺癌防治靶点的潜能。Objective To investigate whether long non-coding RNA Prader-Willi region non-protein coding RNA 1(PWRN1)could regulate the proliferation,invasion and migration of breast cancer cells through phosphatidylin-ositol-3-kinase/serine/threonine kinase(PI3K/Akt)signal pathway.Methods Levels of PWRN1 in normal breast epithelial cell line(MCF10A)and breast cancer cell lines(BT474,BT549,T47D,MCF7,MDA-MB-453,MDA-MB-231)were determined by quantitative reverse transcription-polymerase chain reaction(qPCR)analysis.MDA-MB-231 cells were selected and allocated into blank control group(cells without transfection),negative control group(cells transfected with empty vector pcDNA3.1)and PWRN1 overexpression group(cells transfected with overexpression vector pcDNA3.1-PWRN1).The abilities of proliferation,migration and invasion of MDA-MB-231 cell were analyzed by cell counting(CCK-8)assay,wound healing assay and transwell chamber assay,respectively.Levels of Snail,matrix metallopeptidase-9(MMP-9),phosphorylated phosphatidylinositol 3-kinase(p-PI3K)and phosphorylated serine/threonine kinase 1(p-Akt1)were detected by qPCR and Western blotting.Results PWRN1 was down-regulated in breast cancer cells as compared with MCF-10A cells(P<0.05).Compared with the blank control group and the negative control group,the attenuated proliferation activity(48 h and 72 h)of MDA-MB-231 cells,the decreased wound healing rate and number of transmembrane cells were less,and reduced levels of snail,MMP-9,p-PI3K and p-Akt1 were observed in PWRN1 overexpression group(P<0.05).There was no significant difference in the above indices between the blank control group and the negative control group(P>0.05).Conclusion PWRN1 might inhibit the proliferation,invasion and migration of breast cancer cell through inactivating the PI3K/Akt signal pathway.PWRN1/PI3K/Akt axis has the potential as a target for prevention and treatment of breast cancer.

关 键 词：乳腺癌 Prader-Willi区域非蛋白质编码RNA 1 磷脂酰肌醇-3-激酶/丝氨酸苏氨酸蛋白激酶通路 迁移侵袭 

分 类 号：R737.9[医药卫生—肿瘤]