Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis

Abstract

Hypoxia facilitates the progression of numerous cancers. Circular RNAs (circRNA) have been revealed to be involved in the process of tumors mediated by hypoxia. However, the role and molecular mechanism of circular RNA hsa_circ_0008450 (circ_0008450) in hepatocellular cancer (HCC) under hypoxic conditions has been rarely reported. Expression levels of circ_0008450, microRNA(miR)-431 and A-kinase anchor protein 1 (AKAP1) were examined using reverse transcription-quantitative PCR. Cell viability, apoptosis and glycolysis were assessed via Cell Counting Kit-8, flow cytometry and glycolysis assays, respectively. The association between circ_0008450 or AKAP1 and miR-431 was verified via dual-luciferase reporter assays. Protein levels of AKAP1 were detected by western blotting. Effect of hsa_circ_0008450 on tumor growth in vivo was confirmed by xenograft assays. Circ_0008450 was upregulated in HCC tissues and hypoxia-disposed HCC cells. Depletion of circ_0008450 suppressed tumor growth in vivo and reversed the repression of apoptosis and the acceleration of viability and glycolysis of HCC cells induced by hypoxia treatment in vitro. Notably, circ_0008450 regulated AKAP1 expression by sponging miR-431. Furthermore, miR-431 inhibition reversed the circ_0008450 silencing-mediated effects on viability, apoptosis and glycolysis in hypoxia-treated HCC cells. Additionally, AKAP1 enhancement abolished the effects of miR-431 upregulation on the viability, apoptosis and glycolysis in hypoxia-treated HCC cells. In conclusion, circ_0008450 repression mitigated the progression of HCC under hypoxia by downregulating AKAP1 via miR-431, providing a potential target for HCC treatment.

Circular RNA circ_0061140 accelerates hypoxia-induced glycolysis, migration, and invasion in lung adenocarcinoma through the microRNA-653/hexokinase 2 (HK2) axis

“…Circ_0061140 has been reported as an oncogene in serval human cancers, such as prostate cancer [ 11 ], bladder cancer [ 10 ], endometrial cancer [ 27 ]. In addition, intratumoral hypoxia has been identified as a driving force of tumor progression [ 28 , 29 ], and circRNA could be regulated by hypoxia in tumors [ 30 , 31 ]. In this work, we identified that circ_0061140 level was alerted by hypoxia stimulation, suggesting that circ_0061140 might act as a crucial function in LAUD development under hypoxia.…”

Hypoxia-inducible CircPFKFB4 Promotes Breast Cancer Progression by Facilitating the CRL4DDB2 E3 Ubiquitin Ligase-mediated p27 Degradation

“…For instance, hypoxia-elevated circRNF20 acts as a miR-487a sponge to upregulate the transcription and protein levels of HIF1α, thus promoting the glycolysis and tumorigenesis of BC [26]. Under hypoxia, circ_0008450 facilitates hepatocellular cancer progression by targeting the miR-431/A-kinase anchor protein 1 (AKAP1) axis [27]. Hypoxia-induced ebv-circLMP2A up-regulates HIF1α by interacting with KH-type splicing regulatory protein (KHSRP), leading to angiogenesis of Epstein-Barr virus-associated gastric carcinoma [28].…”

Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma

“…The circ-0051443 from circulating exosomes or HCC tissues regulated BAK1 expression by combining with mir-331-3p to promote cell apoptosis or cell cycle arrest in HCC, and inhibit the biological behavior of HCC cells in vivo or nude mice HCC xenografts[ 100 ]. Another interesting study also showed that has_circ_0008450 expression in HCC tissues or cells might inhibit HCC progression by regulating the mir-214-3p/ezh2 axis[ 101 , 102 ]. These data suggested that specific ncRNAs were useful molecular targets for HCC therapy.…”