Department of Hepatobiliary Surgery, Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, China.
Crit Rev Eukaryot Gene Expr. 2022;32(1):35-47. doi: 10.1615/CritRevEukaryotGeneExpr.2021038907.
Herein, we explored effects of miR-93-5p and gluconeogenic rate-limiting enzyme PCK1 on HCC cells. Bioinformatics analysis and cell experiments confirmed that, compared with expression in normal tissue and cells, miR-93-5p in HCC was abnormally upregulated while PCK1 expression was remarkably downregulated. PCK1 overexpression repressed proliferation, migration, and invasion of HCC cells, and blocked cell cycle in G0/G1 phase. During this process, glucose production was boosted while the production of pyruvate, lactic acid, citric acid, and malic acid was reduced, suggesting that the effect was related to inhibition of glycolysis and induction of gluconeogenic pathways. Elevated miR-93-5p level promoted proliferation, migration, and invasion of HCC cells, accelerated development of cell cycle, activated glycolysis, and suppressed gluconeogenesis. In addition, when miR-93-5p and PCK1 were concurrently upregulated, the abovementioned promoting effects were canceled out. These investigations demonstrated that promoting effect of miR-93-5p on HCC cell growth may be carried out by inhibiting the PCK1 expression, suggesting that miR-93-5p and PCK1 could be applied as new biomarkers or novel therapeutic targets for HCC diagnosis.
在这里，我们探讨了 miR-93-5p 和糖异生限速酶 PCK1 对 HCC 细胞的影响。生物信息学分析和细胞实验证实，与正常组织和细胞中的表达相比，HCC 中的 miR-93-5p 异常上调，而 PCK1 表达显著下调。PCK1 的过表达抑制了 HCC 细胞的增殖、迁移和侵袭，并阻止了细胞周期进入 G0/G1 期。在此过程中，葡萄糖的产生增加，而丙酮酸、乳酸、柠檬酸和苹果酸的产生减少，表明这种作用与抑制糖酵解和诱导糖异生途径有关。升高的 miR-93-5p 水平促进了 HCC 细胞的增殖、迁移和侵袭，加速了细胞周期的发展，激活了糖酵解，抑制了糖异生。此外，当 miR-93-5p 和 PCK1 同时上调时，上述促进作用被抵消。这些研究表明，miR-93-5p 对 HCC 细胞生长的促进作用可能是通过抑制 PCK1 的表达来实现的，提示 miR-93-5p 和 PCK1 可以作为 HCC 诊断的新型生物标志物或治疗靶点。
