The Influence Of Long Non-coding RNA HOTAIR On The Growth And Glucose Metabolism Of Hepatoma

Objective: The development of hepatocellular carcinoma(HCC)is the result of a combination of multiple complex factors.Studies have shown that long non-coding RNA HOX transcript antisense RNA(HOTAIR)is important for the occurrence and development of HCC.Given that glucose metabolic change is one of the most important features of metabolic changes in tumors,so this study aimed to explore the effect of HOTAIR on HCC growth and glucose metabolism,to provide a new direction for the treatment of ACC.Methods: Human normal liver cell line HL-7702 and HCC cell line SMMC-7721 and Hep G-2 were studied.siRNA-HOTAIR and siRNA-scramble vectors were constructed,and lentivirus infected SMMC-7721 and Hep G-2 cells.The experiment was divided into HOTAIR gene silencing experimental group(si-HOTAIR)and scramble gene silencing negative control group(NC).Real-time quantitative fluorescence polymerase chain reaction was used to detect transcriptional levels of HOTAIR,miR-217,relatively glycolytic enzymes glucose-6-phosphate isomerase(GPI),pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA);hypoxia inducible factor-1α(HIF-1α),AXL and epithelial-mesenchymal transition-related factors E-cadherin and vimentin;MTT assay was used to detect tumor cell proliferation;Transwell chamber was performed to detect the abilities of invasion and migration of tumor cells;The glucose and lactate detection kit measured the rate of glucose consumption and the rate of lactic acid production;the western-blot technique was used to detect the expression of GPI,PKM2 and LDHA,HIF-1α,AXL and E-cadherin and vimentin.Results: The expression levels of HOTAIR in SMMC-7721 and Hep G-2 were significantly higher than that in HL-7702.Compared with the negative control group,in si-HOTAIR group of SMMC-7721 and Hep G-2 cell lines,the expression levels of HOTAIR were down-regulated,and the expression levels of miR-217 were up-regulated(P < 0.05),and the proliferations were decreased(P < 0.05).The HOTAIR knockdown in SMMC-7721 and Hep G-2 cells could inhabit the abilities of invasion and migration(P< 0.05),and could decrease the Glucose consumption rates and lactic acid production rates in SMMC-7721 and Hep G-2(P < 0.05).Compared with negative control group,HOTAIR knockdown in SMMC-7721 and Hep G-2 cells could inhabit the expression of glycolysis related enzymes(GPI,PKM2,LDHA)(P < 0.05),HIF-1α,AXL,and vimentin(P < 0.05)in m RNA level,and could increase the expression of E-cadherin(P < 0.05)in m RNA level.Compared with negative control group,HOTAIR knockdown in SMMC-7721 and Hep G-2 cells could inhabit the expression of glycolysis related enzymes(GPI,PKM2,LDHA),HIF-1α,AXL,and vimentin in protein level,and could increase the expressions of E-cadherin in protein level.Conclusion: The expression of HOTAIR in liver cancer cell lines were higher than that of normal liver cell lines and related to the malignant biological behavior of hepatoma.Silencing HOTAIR expression could inhibit the glucose metabolism of hepatoma cells by inhibiting the expression of glycolytic enzymes such as GPI,PKM2,and LDHA.Our results suggested that the influence of HOTAIR on the biological behavior and glucose metabolism of hepatoma may be related to the miR-217/HIF-1α/AXL axis.