miR-148b inhibits glycolysis in gastric cancer through targeting SLC2A1.
miR-148b inhibits glycolysis in gastric cancer through targeting SLC2A1.
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DOI：
10.1002/cam4.1008
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发表时间：
2017-06
期刊：
影响因子：
4
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Ding X;Liu J;Liu T;Ma Z;Wen D;Zhu J
尽管胃癌的分子生物学特征已得到很好的表征，但胃癌的早期诊断生物标志物和有效的治疗方案仍在研究中。在此，我们通过q-PCR分析和原位杂交发现，与匹配的癌旁非肿瘤组织相比，miR-148 b在人胃癌组织中的表达降低。进一步的研究表明，miR-148 b的过表达限制了胃癌细胞系BGC-823和MKN 45中的糖酵解，包括葡萄糖消耗、乳酸产生。生物信息学预测发现，专用转运蛋白溶质载体家族2成员1（SLC 2A 1），也称为GLUT 1，是miR-148 b的直接靶点。通过荧光素酶测定和蛋白质印迹分析进一步证实了靶向效应。此外，与匹配的相邻非肿瘤组织相比，在人GC组织中观察到SLC 2A 1和miR-148 b的相对表达之间存在负相关性。随后，SLC 2A 1 siRNA或特异性抑制剂对SLC 2A 1的抑制限制了miR-148 b介导的糖酵解作用的降低，而SLC 2A 1过表达则消除了miR-148 b对糖酵解的作用。我们的研究结果提供了miR-148 b通过抑制糖酵解在GC发展中的新证据，突出了miR-148 b作为GC治疗新靶点的作用。
Although the molecular biology of GC has been well characterized, early diagnostic biomarkers and effective therapeutic options in gastric cancer are still under investigation. Here, we found that miR‐148b expression decreased in human gastric cancer tissues compared with matched adjacent nontumor tissues by q‐PCR analysis and in situ hybridization. Further investigation revealed that overexpression of miR‐148b limited glycolysis including glucose consumption, lactate production in gastric cancer cell lines BGC‐823 and MKN45. Bioinformatics prediction uncovered that a dedicated transporters solute carrier family 2 member 1 (SLC2A1), also called GLUT1, was the direct target of miR‐148b. The target effects were further confirmed by luciferase assay and western blot analysis. Besides, a reverse correlation was observed between relative SLC2A1 and miR‐148b expression in human GC tissues compared with matched adjacent nontumor tissues. Subsequently, SLC2A1 suppression by SLC2A1 siRNA or specific inhibitor restricted the reduced effects of glycolysis mediated by miR‐148b while SLC2A1 overexpression abrogated the effect of miR‐148b on glycolysis. Our findings provided new evidence of miR‐148b in GC development through restraining glycolysis, highlighting the role of miR‐148b as a new target for GC treatment.