Table_1_CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer.xls

Gastric cancer (GC) remains a major world-wide challenge, especially in Asian countries. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin is used as the first-line treatment and development of chemoresistance is a major cause of progression. UMP/CMP kinase is responsible for the phosphorylation of the ribonucleotide metabolite 5-fluoro-5′-monophosphate (FUMP) in 5-FU metabolic process, and recognized as a key step in the conversion of 5-FU to cytotoxic metabolites. Our bioinformatics analysis and molecular experiments demonstrated that high expression of CMPK1 was associated with prolonged survival and response to 5-FU treatment in GC samples. Further analysis demonstrated that miR-130b as a key epigenetic regulator of CMPK1, and miR-130b-mediated attenuation of CMPK1 resulted in resistance of gastric cancer cells to DNA damage and cell death after treatment with 5-FU. Rescue experiments with augmented CMPK1 expression abolished the effect of miR-130b demonstrating the key function of this miRNA in this pathway. Thus, this newly identified miR-130b-CMPK1 axis suggests a potentially new chemotherapeutic strategy for improved response to 5-FU therapy.

胃腺癌（GC）仍是全球范围内的重大挑战，尤其是在亚洲国家。以5-氟尿嘧啶（5-FU）和顺铂为基础的化疗被视为一线治疗方案，而化疗耐药性的产生则是导致疾病进展的主要原因。UMP/CMP激酶负责在5-FU代谢过程中对核糖核苷酸代谢产物5-氟-5′-单磷酸（FUMP）进行磷酸化，这一过程被认为是5-FU转化为细胞毒代谢物的关键步骤。我们的生物信息学分析和分子实验表明，CMPK1的高表达与胃腺癌样本中5-FU治疗的疗效延长和生存期相关。进一步分析显示，miR-130b作为CMPK1的关键表观遗传调节因子，通过miR-130b介导的CMPK1下调导致胃癌细胞对DNA损伤和治疗后细胞死亡的抗性。增强CMPK1表达的挽救实验消除了miR-130b的效果，证明了该microRNA在此途径中的关键作用。因此，这一新发现的miR-130b-CMPK1轴为5-FU治疗的疗效提升提供了一种潜在的新的化疗策略。