Liu Ning, Dou Lei, Zhang Xinxin
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Pathology, China Medical University, Shenyang, People's Republic of China.
Onco Targets Ther. 2020 Jun 9;13:5283-5291. doi: 10.2147/OTT.S248457. eCollection 2020.
To study the role of LncRNA PTTG3P in colorectal cancer (CRC) and the underlying mechanism.
The expression level of LncRNA PTTG3P was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC cell lines and tumor tissues from 43 CRC patients, and the correlations between LncRNA PTTG3P expression and the clinicopathological indicators and prognosis of CRC patients were analyzed. Then, a PTTG3P knockdown model in CRC cell lines HCT-8 and HCT-116 was constructed. Finally, the relationship between LncRNA PTTG3P and microRNA-155-5p was explored through luciferase reporter experiments and recovery experiments.
qRT-PCR results showed that LncRNA PTTG3P was markedly up-regulated in CRC tumor tissues than that in adjacent tissues. Meanwhile, patients with high LncRNA PTTG3P expression had higher rates of lymph node metastasis and distant metastasis. In addition, cell functional experiments suggested that knocking down PTTG3P markedly reduced the migration abilities of CRC cells. Subsequently, bioinformatics analysis and luciferase reporter gene experiments suggested that LncRNA PTTG3P could directly bind to microRNA-155-5P. Analysis of CRC tissue samples showed that microRNA-155-5P expression was markedly reduced in CRC and was negatively correlated with LncRNA PTTG3P. Finally, the recovery experiments also suggested that there was a mutual regulation between LncRNA PTTG3P and microRNA-155-5P, and silencing microRNA-155-5P can reverse the inhibitory effect of knocking down PTTG3P on the malignant progression of CRC.
In summary, LncRNA PTTG3P level was markedly increased in CRC, and was highly correlated to the incidence of lymph node metastasis and distant metastasis in CRC patients. In addition, LncRNA PTTG3P might promote the ability of CRC to invade and migrate by downregulating microRNA-155-5P. Therefore, dissecting the aberrant regulation of LncRNA PTTG3P/microRNA-155-5P may be valuable for early screening, guidance treatment, and recurrence detection of CRC.
研究长链非编码RNA PTTG3P在结直肠癌（CRC）中的作用及其潜在机制。
采用定量实时聚合酶链反应（qRT-PCR）检测43例CRC患者的CRC细胞系和肿瘤组织中长链非编码RNA PTTG3P的表达水平，并分析长链非编码RNA PTTG3P表达与CRC患者临床病理指标及预后的相关性。然后，构建CRC细胞系HCT-8和HCT-116中的PTTG3P敲低模型。最后，通过荧光素酶报告基因实验和回复实验探究长链非编码RNA PTTG3P与微小RNA-155-5p之间的关系。
qRT-PCR结果显示，CRC肿瘤组织中长链非编码RNA PTTG3P的表达明显高于癌旁组织。同时，长链非编码RNA PTTG3P高表达的患者发生淋巴结转移和远处转移的比例更高。此外，细胞功能实验表明，敲低PTTG3P可显著降低CRC细胞的迁移能力。随后，生物信息学分析和荧光素酶报告基因实验表明，长链非编码RNA PTTG3P可直接与微小RNA-155-5P结合。CRC组织样本分析显示，CRC中微小RNA-155-５P的表达明显降低，且与长链非编码RNA PTTG3P呈负相关。最后，回复实验还表明，长链非编码RNA PTTG3P与微小RNA-155-5P之间存在相互调控关系，沉默微小RNA-155-5P可逆转敲低PTTG3P对CRC恶性进展的抑制作用。
综上所述，CRC中长链非编码RNA PTTG3P水平明显升高，且与CRC患者淋巴结转移和远处转移的发生率高度相关。此外，长链非编码RNA PTTG3P可能通过下调微小RNA-155-5P促进CRC的侵袭和迁移能力。因此，剖析长链非编码RNA PTTG3P/微小RNA-155-5P的异常调控可能对CRC的早期筛查、指导治疗及复发检测具有重要价值。
