Circ-ZDHHC5 Accelerates Esophageal Squamous Cell Carcinoma Progression in vitro via miR-217/ZEB1 Axis

Wang, Qian; Yang, Lili; Fan, Yanxin; Tang, Weiwei; Sun, Handong; Xu, Zhipeng; Zhou, Jian; Zhang, Yanzhou; Zhu, Bin; Cao, Xiufeng

doi:10.3389/fcell.2020.570305

Cited by 24 publications

(23 citation statements)

References 24 publications

(23 reference statements)

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“…Recently, whole-genome sequencing has revealed abnormal expression of several circRNAs in various tumors. Moreover, circRNAs have crucial functions in the genesis and progression of different cancers [48][49][50]. For instance, Zhao et al found that propofol blocked the tumor and aerobic glycolysis of lung cancer cells by regulating the TADA2A/miR-455-3p/FOXM1 axis [51].…”

Section: Discussionmentioning

confidence: 99%

Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma

Liu

Zhang

et al. 2022

Mol Cancer

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Background Although the prognostic outcomes of liver cancer (LC) cases have improved with the advancement in diagnostic technology and treatment methods, the transferability and recurrence of HCC and the 5-year and 10-year survival rates of patients have remained unsatisfactory. As a result, there is a need for more accurate diagnostic indicators that can detect liver cancer early, effectively improving the prognosis of patients. Whole-genome sequencing (WGS) revealed that circ-ZEB1 and PIK3CA are highly expressed in HCC tissues, whereas miR-199a-3p is significantly downregulated in HCC. Multiple databases search and biological analysis revealed that elevated expression of circ-ZEB1 and PIK3CA was related to poor prognosis of HCC. In vitro and in vivo studies revealed that upregulated levels of PIK3CA and circ-ZEB1 were closely associated with HCC proliferation and apoptosis. Based on these results, we believe that circ-ZEB1 and PIK3CA could be used as biomarkers to diagnose and treat patients with HCC. More importantly, circ-ZEB1 can promotes the expression of PIK3CA by silencing miR-199a-3p and affecting the progression of HCC. Methods and results Postoperative specimens from 56 patients with HCC who had not undergone chemotherapy from 2015 to 2018 were collected from the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University. WGS revealed differential expression of genes in HCC. Furthermore, RT-qPCR detected the expression of circ-ZEB1, miR-199a-3p, and PIK3CA in HCC tissues. MTT, EdU, and plate cloning experiments were conducted to detect cell proliferation, whereas flow cytometry analysis was used to detect apoptosis. FISH was used to co-localize circ-ZEB1 and miR-199a-3p, and biotin-coupled probe pull-down assay was used to detect the specific binding of circ-ZEB1 and miR-199a-3p. The dual-luciferase report assay detected the association of miR-199a-3p with PIK3CA. Western blotting was used to study the expression of PIK3CA protein. Circ-ZEB1 and PIK3CA were upregulated in HCC and predicted a poor prognosis. MiR-199a-3p showed low expression in HCC, whereas downregulation of circ-ZEB1 reduced HCC cell proliferation and promoted cell apoptosis. MiR-199a-3p blocked the effect of circ-ZEB1 on HCC. Circ-ZEB1 served as a biomarker of HCC. Circ-ZEB1 promoted the expression of PIK3CA by silencing miR-199a-3p to affect the progress of HCC. Conclusions Circ-ZEB1 promoted the expression of PIK3CA by depleting miR-199a-3p, thereby affecting HCC proliferation and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma

Liu

Zhang

et al. 2022

Mol Cancer

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“…The poor outcome of ESCC is associated with its insidious initial symptoms, susceptibility to metastasis, resistance to radiotherapy, and tumor recurrence ( Pennathur et al, 2013 ). Over the past few years, multidisciplinary and surgical treatments have been developed, but the median survival of ESCC cases is only 10 months ( Wang et al, 2020a ). Moreover, considering the limited prediction of prognosis for ESCC patients, there is an urgent need for the exploration of novel biomarkers.…”

Section: Introductionmentioning

confidence: 99%

A Novel Ferroptosis-Related Biomarker Signature to Predict Overall Survival of Esophageal Squamous Cell Carcinoma

Song

Yan-hu

Gao

et al. 2021

Front. Mol. Biosci.

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Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer (ESCA) type, which is also associated with the greatest malignant grade and low survival rates worldwide. Ferroptosis is recently discovered as a kind of programmed cell death, which is indicated in various reports to be involved in the regulation of tumor biological behaviors. This work focused on the comprehensive evaluation of the association between ferroptosis-related gene (FRG) expression profiles and prognosis in ESCC patients based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419 were selected to develop a novel ferroptosis-related gene signature for GEO and TCGA cohorts. The prognostic risk model exactly classified patients who had diverse survival outcomes. In addition, this study identified the ferroptosis-related signature as a factor to independently predict the risk of ESCC. Thereafter, we also constructed the prognosis nomogram by incorporating clinical factors and risk score, and the calibration plots illustrated good prognostic performance. Moreover, the association of the risk score with immune checkpoints was observed. Collectively, the proposed ferroptosis-related gene signature in our study is effective and has a potential clinical application to predict the prognosis of ESCC.

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“…40 CircZDHHC5 is capable of contributing to ESCC pathogenesis depending on the circZDHHC5/miR-217/zinc finger E-box binding homeobox 1 ceRNA crosstalk. 41 Conversely, circ-Foxo3 shows reduced expression in ESCC and can impede ESCC cell malignant behavior by involving the posttranscriptional modulation of PTEN via miR-23a competition. 42 Considering the anti-ESCC activity of circ_0001946, 14 we sought to explore its ceRNA mechanism in ESCC.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel circ_0001946/miR‐1290/SOX6 ceRNA network in esophageal squamous cell cancer

Wang

Yao

et al. 2022

Thoracic Cancer

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Background Circular RNAs (circRNAs) can function as competing endogenous RNAs (ceRNAs) to impact the development of esophageal squamous cell cancer (ESCC). Human circ_0001946 has been identified as a potential anticancer factor in ESCC, yet our understanding of its molecular basis remains limited. Methods Circ_0001946, microRNA (miR)‐1290 and SRY‐box transcription factor 6 (SOX6) were quantified by quantitative reasl‐time PCR (qRT‐PCR) or immunoblotting. Cell proliferation was assessed by CCK‐8 and EDU assays. Cell apoptosis and invasion were evaluated by flow cytometry and transwell assays, respectively. Cell migration was detected by transwell and wound‐healing assays. The direct relationship between miR‐1290 and circ_0001946 or SOX6 was determined by dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assays were used to assess the role of circ_0001946 in tumor growth. Results Circ_0001946 expression was attenuated in human ESCC, and circ_0001946 increase impeded cell proliferation, invasion, migration and enhanced apoptosis in vitro. Moreover, circ_0001946 increase diminished xenograft growth in vivo. Mechanistically, circ_0001946 bound to miR‐1290, and re‐expression of miR‐1290 reversed circ_0001946‐dependent cell properties. SOX6 was a miR‐1290 target and it was responsible for the regulation of miR‐1290 in cell properties. Furthermore, circ_0001946 functioned as a ceRNA to regulate SOX6 expression via miR‐1290. Conclusion Our findings uncover an undescribed molecular mechanism, the circ_0001946/miR‐1290/SOX6 ceRNA crosstalk, for the anti‐ESCC activity of circ_0001946.

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Circ-ZDHHC5 Accelerates Esophageal Squamous Cell Carcinoma Progression in vitro via miR-217/ZEB1 Axis

Cited by 24 publications

References 24 publications

Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma

Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma

A Novel Ferroptosis-Related Biomarker Signature to Predict Overall Survival of Esophageal Squamous Cell Carcinoma

Identification of a novel circ_0001946/miR‐1290/SOX6 ceRNA network in esophageal squamous cell cancer

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