CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner

Qiu, Shengkui; Li, Bowen; Xia, Yiwen; Xuan, Zhe; Li, Zheng; Xie, Li; Gu, Chao; Lv, Jialun; Chen, Lu; Jiang, Tianlu; Fang, Lang; Xu, Penghui; Yang, Jing; Liu, Ying; Chen, Zetian; Zhang, Lu; Wang, Linjun; Zhang, Diancai; Xu, Hao; Wang, Weizhi; Xu, Zekuan

doi:10.1038/s41419-022-04720-0

Cited by 54 publications

(39 citation statements)

References 38 publications

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“…The TGF-β/SMAD signaling is a classic pathway in cancer metastasis [ 47 ]. The circRNA circTHBS1 , which is highly expressed in GC and associated with poor prognosis, is reported to promote the malignant behaviors and EMT of GC cells by triggering the INHBA/TGF-β pathway [ 48 ]. Mechanistically, circTHBS1 behaves as a miR-204-5p sponge to enhance the INHBA expression, and it also stabilizes the INHBA mRNA mediated by HuR, consequently activating the TGF-β pathway (Fig.…”

Section: Circrnas Participate In Emtmentioning

confidence: 99%

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Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance

Wang

Zhang

Cao

et al. 2022

J Exp Clin Cancer Res

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Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis, primarily caused by metastatic lesions. Improved understanding of GC metastasis at the molecular level yields meaningful insights into potential biomarkers and therapeutic targets. Covalently closed circular RNAs (circRNAs) have emerged as crucial regulators in diverse human cancers including GC. Furthermore, accumulating evidence has demonstrated that circRNAs exhibit the dysregulated patterns in GC and have emerged as crucial regulators in GC invasion and metastasis. However, systematic knowledge regarding the involvement of circRNAs in metastatic GC remains obscure. In this review, we outline the functional circRNAs related to GC metastasis and drug resistance and discuss their underlying mechanisms, providing a comprehensive delineation of circRNA functions on metastatic GC and shedding new light on future therapeutic interventions for GC metastases.

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Section: Circrnas Participate In Emtmentioning

confidence: 99%

“…Mechanistically, circTHBS1 behaves as a miR-204-5p sponge to enhance the INHBA expression, and it also stabilizes the INHBA mRNA mediated by HuR, consequently activating the TGF-β pathway (Fig. 2 AI) [ 48 ]. The circCCDC66 expression is elevated in GC and related to tumor stage and lymphatic metastasis [ 49 ].…”

Section: Circrnas Participate In Emtmentioning

confidence: 99%

Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance

Wang

Zhang

Cao

et al. 2022

J Exp Clin Cancer Res

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“…Although circRNA has a unique closed-loop structure, it still contains miRNA binding sites, which endows it with potential as a miRNA sponge ( 60 – 62 ). This property suggests that circRNAs can inhibit the activity of mature miRNAs, increase the level of endogenous targets, and inhibit miRNAs to regulate the expression of downstream genes ( 63 , 64 ). For example, CIRS-7, which contains more than 70 miRNA seed regions, is considered a ceRNA and plays an important role in a variety of cancers ( 65 , 66 ).…”

Section: Mirna Spongementioning

confidence: 99%

Mechanism underlying circRNA dysregulation in the TME of digestive system cancer

Zhang

et al. 2022

Front. Immunol.

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Circular RNAs (circRNAs) are a new series of noncoding RNAs (ncRNAs) that have been reported to be expressed in eukaryotic cells and have a variety of biological functions in the regulation of cancer pathogenesis and progression. The TME, as a microscopic ecological environment, consists of a variety of cells, including tumor cells, immune cells and other normal cells, ECM and a large number of signaling molecules. The crosstalk between circRNAs and the TME plays a complicated role in affecting the malignant behaviors of digestive system cancers. Herein, we summarize the mechanisms underlying aberrant circRNA expression in the TME of the digestive system cancers, including immune surveillance, angiogenesis, EMT, and ECM remodelling. The regulation of the TME by circRNA is expected to be a new therapeutic method.

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“…Moreover, a few circRNAs have been reported to possess coding potential and can function through circRNA-speci c peptides [8]. As reported, circRNA can exert multiple functions in cancer progression through the combined action of different mechanisms [9][10][11][12][13][14]. For instance, circCD44 promotes triple-negative breast cancer (TNBC) progression via modulation of the miR-502-5p/KRAS and insulin-like growth factor 2 mRNA binding protein 2(IGF2BP2)/Myc axes [12].…”

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confidence: 99%

Exosomal circZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

Chen

Wang

et al. 2022

Preprint

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Background Circular RNAs (circRNAs) have gained attention as novel biomarkers for cancer diagnosis and prognosis. Aberrant expression of circRNAs is widely involved in cancer development, whereas the function and mechanism of novel circRNAs in colorectal cancer (CRC) remain unclear. Methods CircZFR was identified both in CRC tissues from the GEO database and in serum exosomes by competing endogenous RNA (ceRNA) microarray. The expression of circZFR was evaluated in CRC tissues and serum by qRT-PCR and in tissue microarray (TMA) by FISH. The functional roles were confirmed using a series of in vitro assays and tumor xenografts and pulmonary/hepatic metastasis mouse models. The mechanisms of circZFR were assessed through circRNA pulldown, RNA immunoprecipitation (RIP), dual-luciferase reporter assays and rescue experiments. Lastly, TCP1-CD-QDs nanocarrier was used to carry circZFR siRNA (si-circZFR) to exam the therapeutic potential of circZFR in patient-derived xenograft (PDX) models. Results CircZFR was upregulated in cancer tissues and serum exosomes of CRC patients and its level was positively associated to advanced TNM stages and poor prognosis. Serum circZFR was indicative of CRC incidence, advanced-stages and metastasis. Functional experiments demonstrated that circZFR promoted CRC proliferation and metastasis but inhibited apoptosis in vitro and in vivo, exosomes with upregulation of circZFR facilitated growth and migration of cocultured CRC cells. Mechanistically, the generation of circZFR could be improved by epithelial splicing regulatory protein 1 (ESRP1) in CRC cells. CircZFR bound to BCL2-associated transcription factor 1 (BCLAF1) and inhibited its ubiquitinated degradation. Moreover, circZFR sponged miR-3127-5p to increase the expression of rhotekin 2 (RTKN2). Our TCP1-CD-QDs nanocarrier was able to carry si-circZFR and delivered them to the vasculature of CRC tissues and cells, resulting in suppressive tumor growth without obvious adverse effects in PDX models. Conclusions Our findings indicate that ESRP1-mediated circZFR exerts oncogenic effects on CRC development and spread through suppressing BCLAF1 degradation and regulating the miR-3127-5P/RTKN2 axis. CircZFR is a promising serum biopsy marker for CRC diagnosis and an attractive target for further therapy.

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CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner

Cited by 54 publications

References 38 publications

Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance

Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance

Mechanism underlying circRNA dysregulation in the TME of digestive system cancer

Exosomal circZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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