Pisano Andrea, Griñan-Lison Carmen, Farace Cristiano, Fiorito Giovanni, Fenu Grazia, Jiménez Gema, Scognamillo Fabrizio, Peña-Martin Jesùs, Naccarati Alessio, Pröll Johannes, Atzmüller Sabine, Pardini Barbara, Attene Federico, Ibba Gabriele, Solinas Maria Giuliana, Bernhard David, Marchal Juan Antonio, Madeddu Roberto
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
National Institute of Biostructures and Biosystems, 00136 Rome, Italy.
Cancers (Basel). 2020 Nov 19;12(11):3432. doi: 10.3390/cancers12113432.
Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a role in the formation of CSC. We investigated the role of hsa-miR-486-5p (miR-486-5p) in CRC, CSCs, and metastasis, in order to reach a better understanding of the biomolecular and epigenetic mechanisms mir-486-5p-related. The expression of miR-486-5p was investigated in three different matrices from CRC patients and controls and in CSCs obtained from the CRC cell lines HCT-116, HT-29, and T-84. In the human study, miR-486-5p was up-regulated in serum and stool of CRC patients in comparison with healthy controls but down-regulated in tumor tissue when compared with normal mucosa. miR-486-5p was also down-regulated in the sera of metastatic patients. In vitro, miR-486-5p was down-regulated in CSC models and it induced an inhibitory effect on stem factors and oncogenes in the main pathways of CSCs. Our results provide a step forward in understanding the role of mir-486-5p in CRC and CSC, and suggest that further studies are needed to investigate its diagnostic and prognostic power, possibly in combination with other biomarkers.
结直肠癌（CRC）是全球第三大常见癌症，也是癌症死亡的第二大原因。越来越多的证据支持这样一种观点，即患者预后不良与癌症干细胞（CSC）的存在有关，癌症干细胞是一种能够导致癌症复发和转移的细胞群体。微小RNA（miRNA）的失调在癌症干细胞的形成中起作用。我们研究了hsa-miR-486-5p（miR-486-5p）在结直肠癌、癌症干细胞和转移中的作用，以便更好地理解与miR-486-5p相关的生物分子和表观遗传机制。在来自结直肠癌患者和对照的三种不同基质以及从结直肠癌细胞系HCT-116、HT-29和T-84获得的癌症干细胞中研究了miR-486-5p的表达。在人体研究中，与健康对照相比，结直肠癌患者血清和粪便中的miR-486-5p上调，但与正常黏膜相比，肿瘤组织中的miR-486-5p下调。转移性患者血清中的miR-486-5p也下调。在体外，miR-486-5p在癌症干细胞模型中下调，并且对癌症干细胞主要途径中的干细胞因子和癌基因具有抑制作用。我们的结果在理解miR-486-5p在结直肠癌和癌症干细胞中的作用方面向前迈进了一步，并表明需要进一步研究以研究其诊断和预后能力，可能与其他生物标志物联合使用。
