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Novel evidence for oncogenic piRNA-823 as a promising prognostic biomarker and a potential therapeutic target in colorectal cancer.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-06-28 , DOI: 10.1111/jcmm.15537
Junlan Feng 1 , Muqing Yang 1 , Qing Wei 2 , Feifei Song 2 , Youhua Zhang 2 , Xiaodong Wang 1 , Bin Liu 1 , Jiyu Li 1
Affiliation  

piRNA‐823 as a member of the piRNA family is reported to promote tumour cell proliferation in multiple myeloma and hepatocellular cancer. However, few studies on the function of piRNA‐823 in colorectal cancer (CRC). Our present study data showed that piRNA‐823 plays an oncogene role in CRC cells. Inhibition of piRNA‐823 can significantly inhibit the proliferation, invasion and apoptosis resistance of CRC cells. Mechanism studies have shown that piRNA‐823 inhibits the ubiquitination of hypoxia‐inducible factor‐1 alpha (HIF‐1α) by up‐regulating the expression of Glucose‐6‐phosphate dehydrogenase (G6PD) and ultimately up‐regulates the glucose consumption of carcinoma cells and inhibits the content of intracellular reactive oxygen species (ROS). Therefore, we speculate piRNA‐823 promotes the proliferation, invasion and apoptosis resistance of CRC cells by regulating G6PD/HIF‐1α pathway. In this study, we set up the cancer‐promoting function recovery experiment of piRNA‐823 by silencing G6PD gene to confirm the dominance of the above‐mentioned pathways. Using clinical samples, we found that overexpression of piRNA‐823 correlated with poor overall survival and predicted a poor response to adjuvant chemotherapy of patients with CRC. In a word, our research has further enriched the theory of piRNA‐823 promoting the progression of CRC, and laid a solid foundation for the development of piRNA‐823‐based gene therapy for CRC and its use as a promising prognostic biomarker in CRC patients.

中文翻译:

致癌piRNA-823作为结直肠癌有希望的预后生物标志物和潜在治疗靶标的新证据。

据报道,作为piRNA家族成员的piRNA‐823可促进多发性骨髓瘤和肝细胞癌中肿瘤细胞的增殖。但是,关于piRNA-823在结直肠癌(CRC)中的功能的研究很少。我们目前的研究数据表明,piRNA‐823在CRC细胞中起癌基因作用。抑制piRNA‐823可以显着抑制CRC细胞的增殖,侵袭和凋亡抗性。机制研究表明,piRNA‐823通过上调葡萄糖-6磷酸脱氢酶(G6PD)的表达并最终上调癌症的葡萄糖消耗来抑制缺氧诱导因子1α(HIF-1α)的泛素化细胞并抑制细胞内活性氧(ROS)的含量。因此,我们推测piRNA‐823可以促进增殖,通过调节G6PD /HIF-1α途径对CRC细胞的侵袭和凋亡抗性。在这项研究中,我们通过沉默G6PD基因来建立piRNA-823的促癌功能恢复实验,以确认上述途径的优势。使用临床样本,我们发现piRNA‐823的过表达与总体生存期差有关,并预测CRC患者对辅助化疗的反应差。简而言之,我们的研究进一步丰富了piRNA‐823促进CRC进展的理论,并为基于piRNA‐823的CRC基因疗法的开发以及其作为CRC患者有希望的预后生物标志物奠定了坚实的基础。 。我们通过沉默G6PD基因来建立piRNA‐823的促癌功能恢复实验,以确认上述途径的优势。使用临床样本,我们发现piRNA-823的过表达与总体生存期差有关,并预测CRC患者对辅助化疗的反应差。简而言之,我们的研究进一步丰富了piRNA‐823促进CRC进展的理论,并为基于piRNA‐823的CRC基因疗法的开发以及其作为CRC患者有希望的预后生物标志物奠定了坚实的基础。 。我们通过沉默G6PD基因来建立piRNA‐823的促癌功能恢复实验,以确认上述途径的优势。使用临床样本,我们发现piRNA‐823的过表达与总体生存期差有关,并预测CRC患者对辅助化疗的反应差。简而言之,我们的研究进一步丰富了piRNA‐823促进CRC进展的理论,并为基于piRNA‐823的CRC基因疗法的开发以及其作为CRC患者有希望的预后生物标志物奠定了坚实的基础。 。
更新日期:2020-08-11
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