Zhang Kun, Tian Ruoxi, Zhang Wancong, Li Yishuai, Zeng Ning, Liang Yan, Tang Shijie
Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
School of Basic Medicine, Tianjin Medical University, Tianjin, China.
Mol Biol Rep. 2022 Sep;49(9):8241-8250. doi: 10.1007/s11033-022-07540-9. Epub 2022 Aug 4.
The glycolytic enzyme, α-Enolase (ENO1), catalyzes the production of phosphoenolpyruvate from 2-phosphoglycerate, thereby enhancing glycolysis and contributing to tumor progression. In the present study, we aimed to determine the role of ENO1 in skin cutaneous melanoma (SKCM) and the potential underlying mechanism.
The Sangerbox database was used to analyze the mRNA expression of ENO1 in SKCM. Western blotting was used to assess the levels of ENO1, c-Myc, β-catenin, MMP-9, PGAM1, and MMP-13 in SKCM-derived cell lines or tumor tissues from patients with SKCM. The pCMV-SPORT6-ENO1 and pET-28a-ENO1siRNA plasmids were used to overexpress and knockdown ENO1 in SKCM cells, respectively. To determine the function of ENO1 in the malignant behavior of SKCM cells, we performed a wound-healing assay, cell counting kit 8 assay, and transwell chamber analyses. The production of pyruvate and lactic acid in tumor cells was evaluated using their respective kits.
Compared with non-tumor tissues, ENO1 was found to be overexpressed in SKCM tissues. In SKCM cells, ENO1 overexpression promoted invasion, migration, and proliferation of tumor cells; increased pyruvate and lactate production; and increased β-catenin, MMP-9, MMP-13, and c-Myc levels. The opposite effects were observed in SKCM cells silenced for ENO1.
These results indicate that ENO1 is involved in SKCM progression by enhancing the invasion and proliferation of tumor cells. In addition, ENO1 might have an important function in tumor cell glycolysis. Therefore, ENO1 represents a potential therapeutic target for treatment of SKCM.
糖酵解酶α-烯醇化酶（ENO1）催化2-磷酸甘油酸生成磷酸烯醇丙酮酸，从而增强糖酵解并促进肿瘤进展。在本研究中，我们旨在确定ENO1在皮肤黑色素瘤（SKCM）中的作用及其潜在的机制。
使用Sangerbox数据库分析SKCM中ENO1的mRNA表达。采用蛋白质免疫印迹法评估SKCM来源的细胞系或SKCM患者肿瘤组织中ENO1、c-Myc、β-连环蛋白、基质金属蛋白酶-9（MMP-9）、磷酸甘油酸变位酶1（PGAM1）和基质金属蛋白酶-13（MMP-13）的水平。分别使用pCMV-SPORT6-ENO1和pET-28a-ENO1小干扰RNA（siRNA）质粒在SKCM细胞中过表达和敲低ENO1。为了确定ENO1在SKCM细胞恶性行为中的作用，我们进行了伤口愈合试验、细胞计数试剂盒8试验和Transwell小室分析。使用各自的试剂盒评估肿瘤细胞中丙酮酸和乳酸的产生。
与非肿瘤组织相比，ENO1在SKCM组织中过表达。在SKCM细胞中，ENO1过表达促进肿瘤细胞的侵袭、迁移和增殖；增加丙酮酸和乳酸的产生；并提高β-连环蛋白、MMP-9、MMP-13和c-Myc水平。在ENO1沉默的SKCM细胞中观察到相反的效果。
这些结果表明，ENO1通过增强肿瘤细胞的侵袭和增殖参与SKCM进展。此外，ENO1可能在肿瘤细胞糖酵解中具有重要作用。因此，ENO1是治疗SKCM的潜在治疗靶点。
