Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53.
Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53.
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DOI：
10.26355/eurrev_201807_15498
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发表时间：
2018-07
影响因子：
3.3
通讯作者：
H. Wu;Lin Ren;J-Q Xiao;Y. Zhang;X-W Mao;L-F Zhou
中科院分区：
文献类型：
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作者：
H. Wu;Lin Ren;J-Q Xiao;Y. Zhang;X-W Mao;L-F Zhou
目的探讨长非编码RNA-LINP1(LncRNALINP1)在前列腺癌(PCa)中的表达及其可能机制。方法采用实时定量聚合酶链式反应(qRT-PCR)检测74对PCa组织和正常组织中LINP1基因的表达，并分析其表达与PCa病理特征和预后的关系。用qRT-PCR方法验证了lncRNA LINP1在PCa细胞系中的表达。将小干扰RNA(SiRNA)导入PCa细胞系(LNCaP和PC-3)，构建LINP1基因敲除系统。用细胞计数试剂盒-8(CCK-8)、集落形成实验、迁移和侵袭实验评价LINP1的生物学功能。最后，通过Western印迹和qRT-PCR对LINP1的可能机制进行了初步探讨。结果定量逆转录聚合酶链式反应显示LINP1在PCa组织中的表达高于正常组织。与LINP1低表达的PCa患者相比，LINP1高表达患者的肿瘤分期、淋巴转移和远处转移率较高，总生存率较低。转染si-LINP1的细胞增殖、侵袭和转移能力明显低于阴性对照(si-NC)。此外，P53信号通路中的关键蛋白P53、PTEN、Akt和CDK2在LINP1基因敲除后在细胞中的表达显著降低。此外，营救性实验证实LINP1与P53呈负相关。结论LINP1在PCa中表达上调与PCa分期高、有无淋巴转移、远处转移及预后不良有关。此外，LINP1还可通过调节P53信号通路促进Pca的增殖、迁移和侵袭能力。
OBJECTIVE We aim to investigate the expression of long non-coding RNA-LINP1 (lncRNA LINP1) in prostate cancer (PCa) and its potential mechanism. PATIENTS AND METHODS The expression of lncRNA LINP1 in 74 pairs of PCa and normal tissues were detected by quantitative Real-time polymerase chain reaction (qRT-PCR); the relationship between its expression and the pathological features and prognosis of PCa was also analyzed. The expression of lncRNA LINP1 in the PCa cell line was verified by qRT-PCR. Knockdown of LINP1 was constructed by transfection of small interfering RNA (siRNA) in two PCa cell lines (Lncap and PC-3). The biological function of LINP1 was evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, migration and invasion assay, respectively. Finally, the potential mechanism of LINP1 was explored by Western blot and qRT-PCR. RESULTS qRT-PCR results showed a higher expression of LINP1 in PCa than that of normal tissues. Compared with PCa patients with a lower expression of LINP1, those with higher expression had a higher tumor stage, lymphatic metastasis and distant metastasis rate, and lower overall survival rate. Proliferation, invasion and metastasis in cells transfected with si-LINP1 were remarkably decreased than those transfected with negative control (si-NC). Moreover, the expressions of the key proteins in the p53 signaling pathway, including p53, PTEN, Akt and CDK2 were remarkably decreased in cells after knockdown of LINP1. In addition, a negative correlation between LINP1 and p53 was confirmed by rescue experiments. CONCLUSIONS Up-regulated LINP1 in PCa was correlated with a higher PCa stage, lymphatic metastasis, distant metastasis, and worse prognosis. Furthermore, LINP1 could promote the proliferative, migratory and invasive abilities of PCa by regulating the p53-signaling pathway.