lncRNA SNHG12靶向抑制miR-495-3p进而调控PI3K/Akt信号通路对前列腺癌细胞增殖、迁移和侵袭的影响

Effects of IncRNA SNHG12 on the proliferation,migration and invasion of prostate cancer cells by targeting miR-495-3p/PI3K/Akt signaling pathway

目的 探究长链非编码RNA(lncRNA)核仁小分子RNA宿主基因12(SNHG12)靶向抑制miR-495-3p/磷脂肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路对前列腺癌细胞增殖、迁移和侵袭的影响。方法 实时荧光定量PCR(qRT-PCR)检测前列腺癌组织和细胞(LNCaP、C4-2、DU145)中SNHG12、miR-495-3p相对表达水平(将其中的DU145细胞分为si-NC组、si-SNHG12组、si-SNHG12+anti-miR-NC组、si-SNHG12+anti-miR-495-3p组,4组检测);双荧光素酶报告实验检测SNHG12与miR-495-3p靶向关系;MTT法检测细胞增殖;Transwell检测细胞迁移和侵袭;蛋白免疫印迹法(Western blot)检测增殖细胞核抗原(PCNA)、N-钙黏蛋白(N-cadherin)、E-钙黏蛋白(E-cadherin)蛋白相对表达水平。结果 在前列腺癌组织和细胞(LNCaP、C4-2、DU145)中SNHG12相对表达水平明显升高,miR-495-3p相对表达水平明显降低(P<0.05);敲低SNHG12可降低DU145细胞活性、PCNA、N-cadherin蛋白相对表达水平,减少迁移及侵袭细胞数,增加E-cadherin蛋白相对表达水平(P<0.05);SNHG12可靶向负调控miR-495-3p,下调miR-495-3p可逆转敲低SNHG12对前列腺癌细胞增殖、迁移及侵袭的影响。与si-NC组相比,si-SNHG12组p-PI3K、p-Akt蛋白相对表达水平明显降低(P<0.05);与si-SNHG12+anti-miR-NC组相比,si-SNHG12+anti-miR-495-3p组p-PI3K、p-Akt蛋白相对表达水平明显增加(P<0.05)。结论 lncRNA SNHG12可能通过靶向抑制miR-495-3p/PI3K/Akt信号通路促进前列腺癌细胞增殖、迁移和侵袭。

Objective To explore the effects of long non-coding RNA(lncRNA)small nucleolar molecule RNA host gene 12(SNHG12)targetinginhibitionofmiR-495-3p/phospholipinositol-3-kinase(PI3K)/proteinkinaseB(Akt)signaling pathway on the proliferation,migration and invasion of prostate cancer cells.Methods The expressions of SNHG12 and miR-495-3p in prostate cancer tissues and cells(LNCaP,C4-2,DU145)were detected with real-time fluorescence quantitative PCR(qRT-PCR).After DU145 cells were divided into si-NC,si-SNHG12,si-SNHG12+anti-miR-NC and si-SNHG12+anti-miR-495-3p groups,the expressions of SNHG12 and miR-495-3p were detected with qRT-PCR;the targeting relationship between SNHG12 and miR-495-3p was determined with dual luciferase assay;cell proliferation was assessed with MTT assay;cell migration and invasion were evaluated with Transwell assay;the protein expressions of proliferating cell nuclear antigen(PCNA),N-cadherin,and E-cadherin were detected with Western blot.Results The expressions of SNHG12 were significantly increased,while the expression of miR-495-3P was significantly decreased in prostate cancer tissues and cells(LNCaP,C4-2,DU145)(P<0.05).Knockdown of SNHG12 decreased DU145 cell activity,lowered the protein expressions of PCNA and N-cadherin,reduced the number of migrating and invading cells,but increased the protein expression of E-cadherin(P<0.05).SNHG12 targeted and negatively regulated miR-495-3p,and down-regulation of miR-495-3p reversed the effects of SNHG12 knockdown on the proliferation,migration and invasion of prostate cancer cells.Compared with the si-NC group,the si-SNHG12 group had significantly decreased expressions of p-PI3K and p-Akt(P<0.05).Compared with the si-SNHG12+anti-miR-NC group,the si-SNHG12+anti-miR-495-3p group had significantly increased protein expressions of p-PI3K and p-Akt(P<0.05).Conclusion IncRNA SNHG12 can promote the proliferation,migration and invasion of prostate cancer cells through targeted inhibition of miR-495-3p/PI3K/Akt signaling pathway.