LncRNA ZNF674-AS1 Hinders Proliferation and Invasion of Hepatic Carcinoma Cells through the Glycolysis Pathway

Abstract

Purpose. Long noncoding RNAs (lncRNAs) play important roles in regulating various functions of cells at the levels of transcription and posttranscription. Extensive investigations have illustrated that lncRNAs are critical in the glucose metabolism of tumor cells, but their mechanisms of action need to be further explored. This study evaluates the role of lncRNA ZNF674-AS1 on the apoptosis and proliferation of human hepatic carcinoma cells in vitro through the glucose metabolism and its related mechanisms. Methods. Real-time quantitative PCR was employed for detecting the level of expressions for lncRNA ZNF674-AS1 in liver cancer tissues (25 cases), paracancerous tissues, and liver cancer cell lines. The lncRNA ZNF674-AS1 high expression cell strain was constructed by the lentiviral overexpression vector. CCK-8, plate colony formation, transwell assay, lactate production, glucose consumption, and ATP levels were used to detect the change of cell proliferation, colony formation, migration, and invasion, as well as glycolytic capability. Western blot was carried out to detect the expression of HK2, PFKL, PKM2, GLUT1, and PKM1, which are the key proteins of glycolysis in cells. Result. The lncRNA ZNF674-AS1 was undesirably expressed in liver cancer cell lines and tissues. Cell function assessments showed that compared with the blank control group (vector), overexpression of lncRNA ZNF674-AS1 could substantially hinder the proliferation, colony formation, migration, and invasion capability of liver cancer cells. Furthermore, overexpression of lncRNA ZNF674-AS1 could inhibit cell glycolysis (inhibit glucose consumption and reduce intracellular lactate and ATP levels) by inhibiting the expression of key proteins (such as PFKL, HK2, PKM2, and GLUT1) in the process of glycolysis. Conclusion. As a tumor repressor gene, lncRNA ZNF674-AS1 inhibits the expression of key proteins in glycolysis to inhibit glycolysis level, thereby inhibiting cell migration and proliferation. Therefore, lncRNA ZNF674-AS1 could be a potent therapeutic target or a novel diagnostic molecule for patients suffering from liver cancer.

Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review

“…Long noncoding RNA (lncRNA), circular RNA (circRNA) and microRNA targeting PKM2 to affect HCC tumorigenesis and development are one of the current research hotspots. [36,45] noncoding RNA can target PKM2's metabolic enzyme function to affect liver cancer cell metabolic reprogramming, [46][47][48] but also target PKM2's non-metabolic enzyme function to affect HCC tumorigenesis and development. [49,50] Wang C et al [49] found that lncRNA HULC can increase CCND1 expression by miR675-autophagy-PKM2 pathway, further affecting pRB and P21 WAF1/CIP1 expression and increasing liver cancer stem cell proliferation.…”

“…Long noncoding RNA (lncRNA), circular RNA (circRNA) and microRNA targeting PKM2 to affect HCC tumorigenesis and development are one of the current research hotspots. [36,45] noncoding RNA can target PKM2’s metabolic enzyme function to affect liver cancer cell metabolic reprogramming, [46–48] but also target PKM2’s non-metabolic enzyme function to affect HCC tumorigenesis and development. [49,50]…”