The Role Of Circular RNA CircACC1 In Regulating Cell Energy Metabolism

Circular RNAs are a class of RNA molecules that are joined "head to tail" to form a closed loop.In the late 1970s,scientists observed circular RNA molecules in eukaryotic cytoplasm with help of electron microscope.Circular RNAs were regarded as waste products of selective splicing of genes.In recent years,increasing evidences show that Circular RNAs are precisely regulated non-coding RNA with many biological functions.As an important member of the non-coding RNA family,Circular RNAs are gradually attracting researchers' attention.Cancer is one of the major threats to human health.In the long-term struggle with cancers,researchers have been more and more aware of the complexity and diversity of the pathogenesis of tumors.The understanding of tumor has developed from "six hallmarks of cancer" to "ten hallmarks of cancer".Among the four new features,abnormal energy metabolism of tumor cells is included.A number of important proteins have been shown to be involved in the energy metabolism of tumor cells,such as AMPK,which acts as an energy sensor for cells.However,non-coding RNAs,especially Circular RNAs,are rarely reported to be involved in the energy metabolism of tumor cells.As an emerging member of the non-coding RNA family,whether circular RNA is involved in the energy metabolism of tumor cells and its molecular mechanism has not been reported.We explore and discuss this scientific issue in this paper.One important reason why cancers are deadly is their unrestricted rapid proliferation.Uncontrolled development result in low oxygen and low nutrition supply in tumor microenvironment.In order to cope with this adverse situation and provide enough material and energy for tumor cells,tumor cells complete various metabolic reprogramming to provide guarantee for their development.Our study found that,circACCl splicing from key enzyme of fatty acid synthesis gene-acetyl-CoA carboxylase(ACACA).Serum starvation increase the expression of the circACCl.CircACC 1 stabilizes and activates AMPK via promote association of AMPK regulatory subunits ? and ?.Thus accelerates glycolysis and fatty acid ? oxidation to produce more ATP and NADPH to help tumor cells deal with nutrition shortage.The activation effect of circACC1 on AMPK is independent of LKB1,CaMKK2,or TAK1,which is a new pathway for cells to activate AMPK under nutrition deficiency.Data from clinical samples also demonstrated that circACCl expression is correlated with AMPK activation.In summary,our study uncover that circACC1,through regulation of the energy sensor AMPK,realize the transformation of tumor cells from anabolic metabolism to catabolic metabolism under nutritional stress.It is a new evidence that circular RNA is involved in tumor metabolic reprogramming.Also provides a target and idea for the prevention and treatment of clinical cancers.