Sun Shengbai, Li Chaoqun, Cui Kaisa, Liu Bingxin, Zhou Mingyue, Cao Yulin, Zhang Jia, Bian Zehua, Fei Bojian, Huang Zhaohui
Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, China.
Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Front Cell Dev Biol. 2021 Dec 8;9:770006. doi: 10.3389/fcell.2021.770006. eCollection 2021.
Colorectal cancer (CRC) is one of the most common malignancies globally. Increasing evidence indicates that circular RNAs (circRNAs) play a pivotal role in various cancers. The present study focused on exploring the role of a functionally unknown circRNA, hsa_circ_0062682 (circ_0062682), in CRC. By online analyses and experimental validations, we showed that circ_0062682 expression was aberrantly increased in CRC tissues compared with paired normal tissues. Increased expression of circ_0062682 in CRC notably correlated with a poor prognosis and advanced tumor stage. Functional experiments showed that circ_0062682 knockdown reduced CRC growth both and . Mechanistically, we revealed that circ_0062682 could sponge miR-940 and identified D-3-phosphoglycerate dehydrogenase (PHGDH), a key oxidoreductase involved in serine biosynthesis, as a novel target of miR-940. Silencing miR-940 expression could mimic the inhibitory effect of circ_0062682 knockdown on CRC proliferation. The expression of PHGDH was downregulated in circ_0062682-depleted or miR-940 overexpressing CRC cells at both the mRNA and protein levels. Circ_0062682 knockdown suppressed CRC growth by decreasing PHGDH expression and serine production via miR-940. Taken together, these data demonstrate, for the first time, that circ_0062682 promotes serine metabolism and tumor growth in CRC by regulating the miR-940/PHGDH axis, suggesting circ_0062682 as a potential novel therapeutic target for CRC.
结直肠癌(CRC)是全球最常见的恶性肿瘤之一。越来越多的证据表明,环状RNA(circRNA)在各种癌症中发挥着关键作用。本研究聚焦于探索一种功能未知的circRNA,即hsa_circ_0062682(circ_0062682)在结直肠癌中的作用。通过在线分析和实验验证,我们发现与配对的正常组织相比,circ_0062682在结直肠癌组织中的表达异常增加。circ_0062682在结直肠癌中的表达增加与预后不良和肿瘤分期进展显著相关。功能实验表明,敲低circ_0062682可抑制体外和体内的结直肠癌生长。机制上,我们发现circ_0062682可以吸附miR-940,并鉴定出参与丝氨酸生物合成的关键氧化还原酶3-磷酸甘油酸脱氢酶(PHGDH)是miR-940的一个新靶点。沉默miR-940的表达可模拟敲低circ_0062682对结直肠癌增殖的抑制作用。在mRNA和蛋白质水平上,circ_0062682缺失或miR-940过表达的结直肠癌细胞中,PHGDH的表达均下调。敲低circ_0062682通过miR-940降低PHGDH表达和丝氨酸生成,从而抑制结直肠癌生长。综上所述,这些数据首次证明,circ_0062682通过调节miR-940/PHGDH轴促进结直肠癌中的丝氨酸代谢和肿瘤生长,提示circ_0062682作为结直肠癌潜在的新型治疗靶点。