Circular RNA cMTO1 Promotes PTEN Expression Through Sponging miR-181b-5p in Liver Fibrosis

Abstract

Background: Circular RNAs (circRNAs) are considered as key regulators of cancer biology. Recently, cMTO1 (a circRNA derived from MTO1 gene, hsa_circ_0007874) has been demonstrated to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the roles of cMTO1 in liver fibrosis are largely unknown. Methods: Expressions and roles of cMTO1 were examined in vivo and in vitro during liver fibrosis. The interaction between microRNA-181b-5p (miR-181b-5p) and cMTO1 was analyzed by luciferase activity assays and pull down assays. Results: cMTO1 was shown to be reduced in the liver from patients with cirrhosis. In addition, cMTO1 was down-regulated in the mouse fibrotic livers as well as activated hepatic stellate cells (HSCs). Restoring of cMTO1 led to a reduction in HSC proliferation. Results of immunofluorescence analysis showed that cMTO1 suppressed the expressions of α-SMA and type I collagen. cMTO1 was found to be expressed in the cytoplasm of HSCs. Further studies confirmed that cMTO1 and miR-181b-5p were colocated in the cytoplasm. Interestingly, there was an interaction between cMTO1 and miR-181b-5p. Results of luciferase reporter assays and pull down assays confirmed that miR-181b-5p could bind to cMTO1. cMTO1-inhibited HSC activation was blocked down by miR-181b-5p or PTEN. Meanwhile, PTEN was a target of miR-181b-5p. Conclusion: cMTO1 inhibits HSC activation, at least in part, through miR-181b-5pmediated PTEN expression. Our results also suggest that cMTO1 may be a novel therapeutic target in liver fibrosis.

CircAMOTL1 Promotes Tumorigenesis Through miR-526b/SIK2 Axis in Cervical Cancer

“…Non-coding RNAs have been manifested not to be the transcriptional noise, and but to be the important regulatory molecules ( Zhuang et al, 2015 ; Chen et al, 2016 , 2017 ; Li et al, 2016a , b ; Tran et al, 2020 ), and circRNAs are novel endogenous non-coding RNAs that have been identified as owing key regulatory roles in the cancer biology ( Ma et al, 2019 ; Di Agostino et al, 2020 ; Dong et al, 2020 ; Jin et al, 2020 ; Li and Wang, 2020 ; Liu et al, 2020 ; Ou et al, 2020 ; Zhang et al, 2020a ). circRNAs act as important roles in the development and progression of cancers and are involved in various biological processes, such as cell proliferation, apoptosis, and migration by regulating gene expression ( Liu et al, 2019 ; Di Agostino et al, 2020 ; Ji et al, 2020 ; Tang and Chen, 2020 ; Wang et al, 2020c ).…”

“…circRNAs act as important roles in the development and progression of cancers and are involved in various biological processes, such as cell proliferation, apoptosis, and migration by regulating gene expression ( Liu et al, 2019 ; Di Agostino et al, 2020 ; Ji et al, 2020 ; Tang and Chen, 2020 ; Wang et al, 2020c ). Mangy circRNAs have been reported to play important functions in cervical cancers, such as hsa_circ_0000515 ( Tang and Chen, 2020 ), has_ circ_0000388 ( Meng et al, 2020 ), circ-HIPK3 ( Qian and Huang, 2020 ), circ-ITCH ( Li et al, 2020 ; Wu et al, 2020b ), circCLK3 ( Jin et al, 2020 ), etc. However, the role and mechanism of circAMOTL1 in the cervical cancer are thoroughly unclear.…”

“…CircRNAs belong to a special class of non-coding RNA molecules, which are also the latest research hotspots in the field of RNA. Different from linear RNA(with 5′ and 3′ ends), and circRNA molecule has a closed circular structure, that is not affected by RNA exonuclide, and its expression is more stable and not easy to degrade ( Dong et al, 2020 ; Jin et al, 2020 ; Zhang et al, 2020a ). In terms of functions, recent studies reveal that circRNA molecules are rich in microRNA (miRNA) binding sites, and act as a miRNA sponge in cells, thereby removing the inhibition of miRNA on its target genes and increasing the expression level of target genes ( Di Agostino et al, 2020 ; Li and Wang, 2020 ; Liu et al, 2020 ).…”

“…This mechanism of action is called competitive endogenous RNA (ceRNA) mechanism. By interacting with miRNAs associated with diseases, circRNAs play important regulatory roles in diseases ( Dong et al, 2020 ; Jin et al, 2020 ).…”

“…Circular RNA could regulate gene expression at the transcriptional and post-transcriptional levels ( Di Agostino et al, 2020 ; Dong et al, 2020 ; Jin et al, 2020 ; Li and Wang, 2020 ; Liu et al, 2020 ; Zhang et al, 2020a ). CircAMOTL1 is found in human chromosome 11:94532555-94533477 and is upregulated in breast cancer tissues and could promote breast cancer progression ( Ma et al, 2019 ; Ou et al, 2020 ).…”