Shan Yujia, Liu Yuejian, Zhao Lifen, Liu Bing, Li Yang, Jia Li
College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Int J Biochem Cell Biol. 2017 Sep;90:48-58. doi: 10.1016/j.biocel.2017.07.016. Epub 2017 Jul 24.
Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. Aberrant sialylation is crucially involved in the progression of various types of cancer. MicroRNAs (miRNAs) have been broadly studied in cancer. MicroRNA-33a (miR-33a) and Has-let-7e (let-7e) are non-coding RNA that can reduce cell motility and viability in cancer. In this study, miR-33a and let-7e levels were confirmed to be significantly down-regulated in CRC samples (n=32) and drug resistant cell line (HCT-8/5-FU) compared with those in the matched adjacent tissues and drug sensitivity cell line (HCT-8). ST8SIA1 was highly expressed in CRC tissues and HCT-8/5-FU cells, which was negatively correlated with miR-33a/let-7e expression. Luciferase reporter assays confirmed that both miR-33a and let-7e bound to the 3'-untranslated (3'-UTR) region of ST8SIA1. Inhibiting miR-33a/let-7e expression in CRC cells increased endogenous ST8SIA1 mRNA and protein levels. MiR-33a/let-7e knockdown promoted chemoresistance, proliferation, invasion, angiogenesis in vitro, and tumor growth in vivo. Whereas, ectopic expression of miR-33a/let-7e suppressed chemoresistance, proliferation, invasion and angiogenesis in CRC cell lines. ST8SIA1 knockdown mimicked the tumor suppressive effect of miR-33a/let-7e on CRC cells, while restoration of ST8SIA1 abolished the tumor suppressive effect of miR-33a/let-7e on CRC cells. Taken together, altered expression of miR-33a/let-7e was correlated with ST8SIA1 level, which might contribute to CRC progression. The miR-33a/let-7e-ST8SIA1 axis could be a therapeutic target for CRC patients.
结直肠癌（CRC）是全球癌症死亡的主要原因之一。异常的唾液酸化在各种类型癌症的进展中起着关键作用。微小RNA（miRNA）已在癌症领域得到广泛研究。微小RNA-33a（miR-33a）和Has-let-7e（let-7e）是非编码RNA，可降低癌细胞的运动性和活力。在本研究中，与配对的癌旁组织和药物敏感细胞系（HCT-8）相比，miR-33a和let-7e水平在CRC样本（n = 32）和耐药细胞系（HCT-8/5-FU）中被证实显著下调。ST8SIA1在CRC组织和HCT-8/5-FU细胞中高表达，与miR-33a/let-7e表达呈负相关。荧光素酶报告基因检测证实miR-33a和let-7e均与ST8SIA1的3'-非翻译（3'-UTR）区域结合。抑制CRC细胞中miR-33a/let-7e的表达会增加内源性ST8SIA1 mRNA和蛋白水平。敲低miR-33a/let-7e可促进体外化疗耐药、增殖、侵袭、血管生成以及体内肿瘤生长。而miR-33a/let-7e的异位表达可抑制CRC细胞系中的化疗耐药、增殖、侵袭和血管生成。敲低ST8SIA1可模拟miR-33a/let-7e对CRC细胞的肿瘤抑制作用，而恢复ST8SIA1则消除了miR-33a/let-7e对CRC细胞的肿瘤抑制作用。综上所述，miR-33a/let-7e表达的改变与ST8SIA1水平相关，这可能促进CRC的进展。miR-33a/let-
