Zhang Yuexiang, Sun Miao, Chen Yusha, Li Bixun
Department of Comprehensive Internal Medicine, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
College of Pharmacy, Guangxi Medical University, Nanning, China.
Front Pharmacol. 2019 Jul 2;10:741. doi: 10.3389/fphar.2019.00741. eCollection 2019.
Dysregulation of microRNAs (miRNAs) and their targeted downstream genes is involved in the carcinogenesis and progression of colorectal cancer (CRC). miR-519b-3p has been reported to play an important role in several cancers. However, its function in CRC is unclear. In this study, we detected the expression of miR-519b-3p in CRC tissues and cell lines, and determined the potential role of miR-519b-3p in cell proliferation and invasion in CRC. Also, the downstream gene of miR-519b-3p was determined. Our results showed that miR-519b-3p was notably reduced in CRC specimens and cell lines. Overexpression of miR-519b-3p inhibited the proliferation and invasion of RKO and DLD-1 cells, whereas knockdown of miR-519b-3p had the contrary effect. The ubiquitous mitochondrial creatine kinase (uMtCK) was identified as a direct target of miR-519b-3p in CRC using luciferase assay. Additionally, miR-519b-3p expression was negatively correlated with uMtCK expression in CRC specimens. Notably, the miR-519b-3p suppressed the uMtCK/Wnt signaling pathway in CRC cells, thereby suppressing CRC cell proliferation and invasion. The inhibition of uMtCK by miR-519b-3p may provide a promising option for the treatment of CRC.
微小RNA(miRNA)及其靶向的下游基因的失调参与了结直肠癌(CRC)的发生和发展。据报道,miR-519b-3p在多种癌症中发挥重要作用。然而,其在结直肠癌中的功能尚不清楚。在本研究中,我们检测了结直肠癌组织和细胞系中miR-519b-3p的表达,并确定了miR-519b-3p在结直肠癌细胞增殖和侵袭中的潜在作用。此外,还确定了miR-519b-3p的下游基因。我们的结果表明,miR-519b-3p在结直肠癌标本和细胞系中显著降低。miR-519b-3p的过表达抑制了RKO和DLD-1细胞的增殖和侵袭,而敲低miR-519b-3p则产生相反的效果。使用荧光素酶报告基因检测法,在结直肠癌中确定普遍存在的线粒体肌酸激酶(uMtCK)是miR-519b-3p的直接靶点。此外,在结直肠癌标本中,miR-519b-3p表达与uMtCK表达呈负相关。值得注意的是,miR-519b-3p抑制了结直肠癌细胞中的uMtCK/Wnt信号通路,从而抑制了结直肠癌细胞的增殖和侵袭。miR-519b-3p对uMtCK的抑制作用可能为结直肠癌的治疗提供一个有前景的选择。