Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, 100875, China.
Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, 100048, China.
Sci China Life Sci. 2018 May;61(5):541-549. doi: 10.1007/s11427-017-9138-9. Epub 2018 Jan 2.
Late-stage melanoma is refractory to current therapies. MicroRNAs (miRNAs) can modulate many physiological and pathological processes of melanoma. Studies have demonstrated that miR-137 acts as a tumor suppressor by inhibiting the proliferation of melanoma cells through targeting multiple mRNAs. The glyoxalase system member glyoxalase 1 (GLO1) is the principal scavenging enzyme of methylglyoxal (MG), a toxic byproduct of glycolysis. Using S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD), we found that miR-137 downregulated the expression of GLO1 in melanoma cells. Bioinformatics analysis predicted that GLO1 is a direct target of miR-137. This was validated by dual luciferase reporter assay. Quantitative RT-PCR (qRT-PCR) and western blot analysis indicated that miR-137 could decrease endogenous GLO1 expression. Furthermore, siRNA targeting of GLO1 mimicked inhibition of melanoma cell proliferation caused by miR-137 overexpression. Re-expression of GLO1 was able to restore miR-137-mediated suppression of melanoma cell proliferation. Therefore, these results suggest that miR-137 inhibits the proliferation of melanoma cells by targeting GLO1.
晚期黑色素瘤对目前的治疗方法具有抗药性。MicroRNAs（miRNAs）可以调节黑色素瘤的许多生理和病理过程。研究表明，miR-137 通过靶向多个 mRNAs 抑制黑色素瘤细胞的增殖，从而发挥肿瘤抑制作用。糖氧还蛋白系统成员糖氧还蛋白 1（GLO1）是甲基乙二醛（MG）的主要清除酶，MG 是糖酵解的有毒副产物。使用体内/体外标记分析动态蛋白质组学（SiLAD），我们发现 miR-137 在黑色素瘤细胞中下调 GLO1 的表达。生物信息学分析预测 GLO1 是 miR-137 的直接靶标。双荧光素酶报告基因检测实验验证了这一点。定量 RT-PCR（qRT-PCR）和 Western blot 分析表明 miR-137 可以降低内源性 GLO1 的表达。此外，靶向 GLO1 的 siRNA 模拟了 miR-137 过表达引起的黑色素瘤细胞增殖抑制。GLO1 的重新表达能够恢复 miR-137 介导的黑色素瘤细胞增殖抑制。因此，这些结果表明 miR-137 通过靶向 GLO1 抑制黑色素瘤细胞的增殖。
