Hong Sen, Yan Zhenkun, Wang Helei, Ding Lei, Bi Miaomiao
Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China.
Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun 130022, Jilin China.
Biosci Rep. 2019 Aug 13;39(8). doi: 10.1042/BSR20191123. Print 2019 Aug 30.
To investigate the role of microRNA-497-5p (miR-497-5p) in the tumorigenesis of colorectal cancer (CRC), the present study applied qRT-PCR to detect the expression level of miR-497-5p in both clinical samples and CRC cell lines. Furthermore, to specifically evaluate the carcinogenic role of miR-497-5p in CRC, the expression of miR-497-5p was monitored by transfecting with the mimics or inhibitors of miR-497-5p. Transwell assay as well as CCK-8 assay were used to determine the functions of miR-497-5p on cell invasion, migration and proliferation, respectively. miR-497-5p expression was remarkably down-regulated in clinical samples with cancer development as well as in CRC cell lines. Additionally, low miR-497-5p expression was remarkably correlated with higher TNM stage and lymph node metastasis of CRC patients. Up-regulation of miR-497-5p significantly inhibited proliferation, migration, and invasion of LOVO CRC cell line. Conversely, antagonizing miR-497-5p significantly promoted cell proliferation, migration and invasion. Mechanistic analysis revealed that miR-497-5p directly bound to its downstream target, protein tyrosine phosphatase non-receptor type 3 (PTPN3), whose aberrant expression partially reversed inhibition of cell proliferation and migration. Taken together, the present study elucidated the inhibitory role of miR-497-5p in CRC via targeting PTPN3, which potentiated miR-497-5p as a potential therapeutic target for combating CRC.
为了研究微小RNA-497-5p(miR-497-5p)在结直肠癌(CRC)肿瘤发生中的作用,本研究应用qRT-PCR检测临床样本和CRC细胞系中miR-497-5p的表达水平。此外,为了具体评估miR-497-5p在CRC中的致癌作用,通过转染miR-497-5p的模拟物或抑制剂来监测miR-497-5p的表达。分别采用Transwell试验和CCK-8试验来确定miR-497-5p对细胞侵袭、迁移和增殖的作用。miR-497-5p的表达在癌症进展的临床样本以及CRC细胞系中显著下调。此外,低miR-497-5p表达与CRC患者较高的TNM分期和淋巴结转移显著相关。miR-497-5p的上调显著抑制了LOVO CRC细胞系的增殖、迁移和侵袭。相反,拮抗miR-497-5p显著促进细胞增殖、迁移和侵袭。机制分析表明,miR-497-5p直接与其下游靶点非受体型蛋白酪氨酸磷酸酶3(PTPN3)结合,PTPN3的异常表达部分逆转了对细胞增殖和迁移的抑制。综上所述,本研究阐明了miR-497-5p通过靶向PTPN3在CRC中的抑制作用,这使miR-497-5p成为对抗CRC的潜在治疗靶点。