长链非编码 RNA LINP1 通过吸附 microRNA-491-3p 促进胰腺癌的恶性进展。
LncRNA LINP1 promotes malignant progression of pancreatic cancer by adsorbing microRNA-491-3p.
机构信息
Department of Oncology, Liaocheng Infectious Disease Hospital, Liaocheng, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Sep;24(18):9315-9324. doi: 10.26355/eurrev_202009_23013.
OBJECTIVE
The purpose of this study was to explore the mechanism by which long noncoding RNA (lncRNA) LINP1 promoted the development of pancreatic cancer (PCa). Meanwhile, the regulatory relationship between lncRNA LINP1 and microRNA-491-3p was further investigated to provide an effective theoretical basis for the treatment of this cancer.
PATIENTS AND METHODS
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to examine lncRNA LINP1 and microRNA-491-3p expression in tumor tissue specimens collected from 56 PCa patients, and the interplay between lncRNA LINP1 expression and some clinical indicators, as well as prognosis of patients with PCa was also analyzed. Meanwhile, in vitro, qRT-PCR further verified lncRNA LINP1 level in PCa cell lines. In addition, lncRNA LINP1 knockdown model was constructed using lentivirus in PCa cell lines CFPAC-1 and BxPC-3, and Cell Counting Kit-8 (CCK-8), transwell, and cell wound healing assays were carried out to evaluate the impact of lncRNA LINP1 on the function of PCa cells. Finally, Dual-Luciferase reporting assay and cell reverse experiments were applied to uncover the potential mechanism.
RESULTS
QRT-PCR revealed that lncRNA LINP1 showed a significantly higher expression in pancreatic tumor tissue samples than in adjacent normal ones. Compared with patients with low expression of lncRNA LINP1, patients with highly expressed lncRNA LINP1 showed a higher incidence of distant metastasis, but a lower overall survival rate. In addition, compared to the sh-NC group, the proliferation, invasion, and migration ability of PCa cells decreased remarkably in LINP1 knockdown group. The results of Luciferase reporting assay demonstrated that lncRNA LINP1 could be targeted by microRNA-491-3p through a specific binding site, and qRT-PCR results uncovered a negative correlation between microRNA-491-3p and lncRNA LINP1 expression in PCa tissues. Finally, the recovery experiment revealed a mutual regulation between LINP1 and microRNA-491-3p, which may jointly regulate the malignant progression of PCa.
CONCLUSIONS
LncRNA LINP1 is able to enhance the proliferation and metastasis of PCa cells by modulating microRNA-491-3p, thus affecting the incidence of lymph node or distant metastasis and prognosis of patients with PCa.
目的
本研究旨在探讨长链非编码 RNA（lncRNA）LINP1 促进胰腺癌（PCa）发展的机制。同时，进一步研究 lncRNA LINP1 与 microRNA-491-3p 之间的调控关系，为治疗这种癌症提供有效的理论依据。
患者和方法
采用实时荧光定量聚合酶链反应（qRT-PCR）检测 56 例 PCa 患者肿瘤组织标本中 lncRNA LINP1 和 microRNA-491-3p 的表达，并分析 lncRNA LINP1 表达与部分临床指标及 PCa 患者预后的关系。同时，在体外通过 qRT-PCR 进一步验证 PCa 细胞系中 lncRNA LINP1 的水平。此外，采用慢病毒构建 PCa 细胞系 CFPAC-1 和 BxPC-3 的 lncRNA LINP1 敲低模型，并通过细胞计数试剂盒-8（CCK-8）、Transwell 和细胞划痕愈合实验评估 lncRNA LINP1 对 PCa 细胞功能的影响。最后，应用双荧光素酶报告实验和细胞反向实验揭示潜在机制。
结果
qRT-PCR 显示，lncRNA LINP1 在胰腺肿瘤组织标本中的表达明显高于邻近正常组织。与 lncRNA LINP1 低表达的患者相比，lncRNA LINP1 高表达的患者远处转移发生率更高，但总生存率更低。此外，与 sh-NC 组相比，LINP1 敲低组 PCa 细胞的增殖、侵袭和迁移能力明显降低。荧光素酶报告实验结果表明，lncRNA LINP1 可通过特定结合位点被 microRNA-491-3p 靶向，qRT-PCR 结果显示 PCa 组织中 microRNA-491-3p 与 lncRNA LINP1 表达呈负相关。最后，恢复实验揭示了 LINP1 和 microRNA-491-3p 之间的相互调节作用，它们可能共同调节 PCa 的恶性进展。
结论
lncRNA LINP1 通过调节 microRNA-491-3p 增强 PCa 细胞的增殖和转移能力，从而影响 PCa 患者的淋巴结或远处转移发生率和预后。
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