Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou.
Department of Pathology, Affiliated Hospital of Panzhihua University, Panzhihua.
Anticancer Drugs. 2021 Jun 1;32(5):508-516. doi: 10.1097/CAD.0000000000001069.
miR-206 plays an essential role in repressing the growth of multiple cancer cells. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. However, it is mostly unknown whether G6PD is associated with miR-206-mediated growth repression of hepatocellular carcinoma (HCC) cells. In this study, we found that the expression of G6PD was upregulated in HCC patients and cell lines, whereas the expression of miR-206 was negatively associated with the clinical staging criterion of primary liver cancer. Overexpression of G6PD increased lipid accumulation and promoted cell proliferation. Conversely, inhibition of G6PD expression decreased lipid accumulation and suppressed cell proliferation. Moreover, miR-206 could directly bind to G6PD mRNA 3´-UTR and downregulate G6PD level. Overexpression of G6PD significantly attenuated the miR-206 mimic-mediated suppression of lipid accumulation and cell proliferation. In summary, the results demonstrated that miR-206 could inhibit lipid accumulation and growth of HCC cells by targeting G6PD, suggesting that the miR-206-G6PD axis may be a promising target for treating HCC.
miR-206 在抑制多种癌细胞生长中发挥重要作用。葡萄糖-6-磷酸脱氢酶（G6PD）是戊糖磷酸途径的限速酶。然而，G6PD 是否与 miR-206 介导的肝癌（HCC）细胞生长抑制有关，这在很大程度上尚不清楚。在本研究中，我们发现 G6PD 的表达在 HCC 患者和细胞系中上调，而 miR-206 的表达与原发性肝癌的临床分期标准呈负相关。G6PD 的过表达增加了脂质积累并促进了细胞增殖。相反，抑制 G6PD 的表达减少了脂质积累并抑制了细胞增殖。此外，miR-206 可以直接结合 G6PD mRNA 3´-UTR 并下调 G6PD 水平。G6PD 的过表达显著减弱了 miR-206 模拟物介导的脂质积累和细胞增殖的抑制作用。综上所述，这些结果表明，miR-206 通过靶向 G6PD 抑制 HCC 细胞的脂质积累和生长，提示 miR-206-G6PD 轴可能是治疗 HCC 的有前途的靶点。
