Circular RNA AKT3 governs malignant behaviors of esophageal cancer cells by sponging miR-17-5p

Zang, Huidong; Ji, Fujian; Ju, Haiying; Tian, Xiaofeng

doi:10.3748/wjg.v27.i3.240

Cited by 13 publications

(10 citation statements)

References 29 publications

(20 reference statements)

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“…Using TargetScan, an online prediction software, AKT3 and HDAC1 were identified as potential target genes of miR-3614-3p, in which AKT, also known as PKB, is vital for maintaining normal cellular function. Concerning its potential role in cancer, previous studies have identified a correlation between tumor development and AKT3 expression ( 16 - 20 ). Wang et al ( 21 ) verified that miR-384 could significantly suppress the proliferation of colorectal cancer by targeting AKT3 , and that miRNA-433 targets AKT3 , thereby inducing the inhibition of cell proliferation and viability in BC ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

miR-3614-3p suppresses cell aggressiveness of human breast cancer by targeting AKT3 and HDAC1 expression

Wang¹,

Jing²,

Li³

et al. 2022

Transl Cancer Res TCR

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Background MicroRNAs (miRNAs) regulate various pathophysiological functions and pathobiological progression in various cancers. Our recent study reported that miR-3614-3p significantly suppressed the proliferation of breast cancer (BC) cells by downregulating its host gene TRIM25 . However, other functional roles of miR-3614-3p migration and invasion in BC and its potential mechanisms are not clearly elucidated. Methods In this study, we investigated miR-3614-3p regulation of AKT3 and HDAC1 expression in BC. miR-3614-3p and AKT3/HDAC1 mRNA expression levels were determined using quantitative real-time PCR (qRT-PCR) in MCF-7 and MDA-MB-231 BC cells. The effects of miR-3614-3p on migration and invasion were measured using wound healing and transwell migration assays. In BC cells, miR-3614-3p levels were remarkably low, and AKT3 and HDAC1 mRNA and protein levels were high as assessed by qRT-PCR and western blot. Finally, we investigated the role of AKT3/HDAC1 using silent interfering RNA (siRNA) and confirmed the targeting of AKT3 and HDAC1 3' UTR through miR-3614-3p using a luciferase reporter assay. Results In the present study, we found that overexpression of miR-3614-3p markedly suppressed tumor cell invasion and migration independent of TRIM25 , whereas other target genes, AKT3 and HDAC1 , were involved. Moreover, we found that the resulting silencing of AKT3 and HDAC1 suppressed cell migration. Conclusions miR-3614-3p is an anti-oncogene that can suppress BC cells by targeting AKT3 and HDAC1 , revealing the potential role of miR-3614-3p in suppressing BC metastasis. Therefore, miR-3614 may act as a potential biomarker for BC prognosis.

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Section: Discussionmentioning

confidence: 99%

miR-3614-3p suppresses cell aggressiveness of human breast cancer by targeting AKT3 and HDAC1 expression

Wang¹,

Jing²,

Li³

et al. 2022

Transl Cancer Res TCR

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“…circ-AKT3 (Figure 4) derives from the AKT3 gene and was identified in gastric cancer cells with cis-Pt resistance (77). Circ-AKT3 was found to be overexpressed in ESCC and induced proliferation, migration and invasion of TE-1 ESCCs (78). circ-AKT3 knockdown suppressed TG of TE-1 ESCCs in nude mice (78).…”

Section: Circrnas Can Modulate the Activity Of Oncogenes And Tumor Su...mentioning

confidence: 99%

Circular RNAs With Efficacy in PreclinicalIn VitroandIn VivoModels of Esophageal Squamous Cell Carcinoma

Weidle

Sela

Brinkmann

et al. 2022

Cancer Genomics Proteomics

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Esophageal cancer is associated with a dismal prognosis. The armamentarium of approved drugs is focused on chemotherapy with modest therapeutic benefit. Recently, checkpoint inhibitory monoclonal antibody Pembrolizumab was approved. In order to identify new targets and modalities for the treatment of esophagus squamous cell carcinoma (ESCC) we searched the literature for circRNAs involved in the pathogenesis of ESCC. We identified two down-regulated and 17 up-regulated circRNAs as well as a synthetic circRNA with efficacy in preclinical in vivo systems. Down-regulated circRNAs sponge microRNAs directed against tumor suppressor genes. Up-regulated circRNAs sponge microRNAs directed against mRNAs, which encode proteins with pro-tumoral functions. We discuss issues such as reconstitution of down-regulated circRNAs and inhibition of up-regulated circRNAs with short interfering RNA (siRNA)-related entities. Also, we address druggability issues of the identified targets.Esophageal carcinoma is the seventh most common cancer worldwide with 570,000 cases annually (1). Two major histological sub-types are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCCs arise in squamous cells that line the esophagus, whereas EACs derive from glandular cells of the esophagus (2). The ratio of incidence between ESCC and EAC depends on the geographic location with ESCC emerging as the most frequent subtype worldwide (3). Therapies such as endoscopic resection, surgery, chemo-and radio-therapy and treatment with immune-checkpoint inhibitory monoclonal antibodies (mAbs) only confer minimal survival advantages (4-7). Among the agents under development are epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor (VEGFR), hepatocyte growth factor (HGF)-tyrosine protein kinase c-MET and fibroblast growth factor receptor 2 (FGFR2) signaling inhibitors in the format of mAbs or small molecule tyrosine kinase inhibitors (4) as well as small molecule inhibitors of mechanistic target of rapamycin (mTOR), poly(ADP)ribose-polymerase 1 (PARP1) and cyclindependent kinases (CDKs) (8-10), most of them affecting rat sarcoma (RAS), rapidly accelerated firbrosarcoma (RAF), extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase(MAPK), phosphoinosite-3-kinase (PI3K), serine-threonine kinase AKT and mTOR pathways.Despite these ongoing efforts, identification of new targets and treatment modalities for ESCC is an issue of high priority. In this review, we focus on circRNAs with documented efficacy in preclinical efficacy in in vivo models for treatment of ESCC. Circular RNASeveral types of non-coding RNAs such as t-RNA, r-RNA, siRNA, lncRNA and circRNA have been described (11). CircRNAs are covalently closed circles of RNA and are products of backsplicing events in which one exon is spliced to a preceding exon (12). A unique junction is generated which allows their specific detection by molecular probes (12). At least 30000 circRNA...

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“…circAKT3 increases EC cell proliferation, migration, and invasion by decreasing miR-17-5p activity and indirectly facilitating STAT3 and RHOC activity. circAKT3 knockdown decreased EC tumor growth in vivo , suggesting that it could be a target of further study to improve our understanding of the underlying processes in the development and progression of EC ( 165 ).…”

Section: Regulation Of Stat3 In Ecmentioning

confidence: 99%

Molecular mechanism, regulation, and therapeutic targeting of the STAT3 signaling pathway in esophageal cancer (Review)

et al. 2022

Int J Oncol

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Circular RNA AKT3 governs malignant behaviors of esophageal cancer cells by sponging miR-17-5p

Cited by 13 publications

References 29 publications

miR-3614-3p suppresses cell aggressiveness of human breast cancer by targeting AKT3 and HDAC1 expression

miR-3614-3p suppresses cell aggressiveness of human breast cancer by targeting AKT3 and HDAC1 expression

Circular RNAs With Efficacy in PreclinicalIn VitroandIn VivoModels of Esophageal Squamous Cell Carcinoma

Molecular mechanism, regulation, and therapeutic targeting of the STAT3 signaling pathway in esophageal cancer (Review)

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