A novel circulating RNA circELMOD3 functions as a tumor suppressor in hepatocellular carcinoma through TRIM13/P53 signal axis

Abstract

Background Circular RNAs (circRNAs) have been identified as key regulatory factors in tumor development based on accumulating studies. However, the underlying molecular mechanisms of the circulating circRNAs in hepatocellular carcinoma (HCC) haven't t been fully elucidated. Methods Five pairs of HCC and adjacent normal tissues were processed using RNA-sequencing to determine the differential expressed circRNAs. The expression levels of genes and proteins were detected by qPCR and Western blotting, respectively. CCK-8, EdU, Flow cytometry, wound healing assay, Transwell assays, and xenograft mouse model were performed to investigate the biological function of circELMOD3 both in vitro and in vivo. Fluorescence in situ hybridization (FISH), RNA antisense purification (RAP) and dual luciferase reporter assay were carried out to verify the interaction between circELMOD3, miR-6864-5P and TRIM13. Results CircELMOD3 was downregulated in plasma and tissues from HCC patients and was related to their clinicopathological characteristics. Significantly, plasma circELMOD3 was shown to be a highly sensitive and non-invasive biomarker to distinguish HCC from healthy controls (AUC = 0.908). Functionally, circELMOD3 prevented HCC cells from proliferating and caused them to undergo apoptosis both in vitro and in vivo. Mechanistically, circELMOD3 increased the expression of TRIM13 by acting as a sponge for miR-6864-5P. In addition, overexpression of circELMOD3 lead to enhanced stability and higher expression level of TRIM13 mRNA, to which it directly binds, and in turn activated the P53 signaling pathway. Conclusion CircELMOD3 plays a tumor suppressor role in HCC via TRIM13/P53 signaling axis, which can serve as a potential target for early diagnosis and treatment of HCC patient.

circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA

“…Currently, circRNA studies have focused mainly on their function as a miRNA sponge, while other biological functions and potential molecular mechanisms still need to be further investigated. Our group has previously studied the direct binding of circRNAs to mRNAs [15,28,29]. On this basis, we investigated whether circSORBS1 can directly bind to mRNAs to regulate their protein expression while indirectly inhibiting mRNA degradation by acting as a miRNA sponge.…”