Hepatic stellate cell exosome-derived circWDR25 promotes the progression of hepatocellular carcinoma &lt;i&gt;via&lt;/i&gt; the miRNA-4474-3P-ALOX-15 and EMT axes

Liu, Lei; Liao, Rui; Wu, Zhongjun; Du, Changsheng; You, Yu; Que, Keting; Duan, Yu-Xin; Yin, Kun-Li; Ye, Wentao

doi:10.5582/bst.2022.01281

Cited by 26 publications

(24 citation statements)

References 43 publications

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“…[45][46][47] circRNAs can also affect the apoptosis of cancer cells and thus affect the programmed cell death of HCC, 48,49 or influence HCC invasion and metastasis by affecting the epithelial-to-mesenchymal transition (EMT). 50,51 Here, in vitro and in vivo experiments manifested that circSLC39A5 inhibited the proliferation, migration, and invasion of HCC cells, promoted cells apoptosis, and was associated with low expression of proliferation index Ki67 and capillarity marker CD34. Notably, it has been reported that CD34 + endothelium-coated tumor clusters can be released into the bloodstream to accelerate extrahepatic metastasis via an EMTindependent pathway.…”

Section: Discussionmentioning

confidence: 92%

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

Liu,

Lai,

et al. 2023

Cancer Science

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Accumulating evidence indicates that circular RNAs (circRNAs) are inextricably linked to cancer development. However, the function and mechanism of nucleus‐localized circRNAs in hepatocellular carcinoma (HCC) still require investigation. Here, qRT‐PCR and receiver‐operating characteristic curve were used to detect the expression and diagnostic potential of circSLC39A5 for HCC. The biological function of circSLC39A5 in HCC was investigated in vitro and in vivo. Nucleoplasmic separation assay, fluorescence in situ hybridization, RNA pulldown, RNA immunoprecipitation, the HDOCK Server, the NucleicNet Webserver, crosslinking‐immunoprecipitation, MG132 treatment, and chromatin immunoprecipitation were utilized to explore the potential molecular mechanism of circSLC39A5 in HCC. The results showed that circSLC39A5 was downregulated in both HCC tissues and plasma and was associated with satellite nodules and lymph node metastasis/vascular invasion. CircSLC39A5 was stably expressed in plasma samples under different storage conditions, showing good diagnostic potential for HCC (AUC = 0.915). CircSLC39A5 inhibited proliferation, migration, and invasion, facilitated the apoptosis of HCC cells, and was associated with low expression of Ki67 and CD34. Remarkably, circSLC39A5 is mainly localized in the nucleus and binds to the transcription factor signal transducer and activator of transcription 1 (STAT1), affecting its stabilization and expression. STAT1 binds to the promoter of thymine DNA glycosylase (TDG). Overexpression of circSLC39A5 elevates TDG expression and reverses the increase of proliferating cell nuclear antigen (PCNA) expression and the overactive cell proliferation caused by TDG silencing. Our findings uncovered a novel plasma circRNA, circSLC39A5, which may be a potential circulating diagnostic marker for HCC, and the mechanism by which nucleus‐localized circSLC39A5 exerts a transcriptional regulatory role in HCC by affecting STAT1/TDG/PCNA provides new insights into the mechanism of circRNAs.

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Section: Discussionmentioning

confidence: 92%

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

Liu,

Lai,

et al. 2023

Cancer Science

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“…Exosomes have been implicated in physiological and pathological processes, such as angiogenesis [ 18 ], immune responses [ 23 ], homeostasis maintenance [ 24 ], coagulation [ 25 ], inflammation [ 26 ], cancer progression [ 27 ], and antigen presentation [ 28 ]. Nucleic acids, proteins, and metabolites delivered by exosomes into recipient cells effectively alter their biological response [ 12 ].…”

Section: Exosomes: a Means Of Intercellular Communicationmentioning

confidence: 99%

“…CircRNA was once considered as the noise of transcription but has attracted increasing attention in recent years. The results of several research teams have identified many important roles of multiple circRNAs in HCC [ 18 , 23 , 27 ].…”

Section: Circrna: An Important Regulatory Factor In Hccmentioning

confidence: 99%

“…Wang et al [ 52 ] found that exosomes derived from highly metastatic cells (HCCLM3) promote the migration and invasion of nonmetastatic cells (HepG2) and low metastatic cells (MHCC-97L) via the circPTGR1/miR449a/MET axis. Hepatic stellate cell (HSC)-derived exosomes could transmit circWDR25, ultimately inducing an EMT in the TME via the circWDR25/miR-4474-3p/ALOX15 axis [ 27 ].…”

Section: An Excellent Combination Of Exosomes and Circrnasmentioning

confidence: 99%

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Exosomes and circular RNAs: promising partners in hepatocellular carcinoma from bench to bedside

Xue

Jiang

et al. 2023

Discov Onc

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Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, and a low 5-year survival rate. Exploring the potential molecular mechanisms, finding diagnostic biomarkers with high sensitivity and specificity, and determining new therapeutic targets for HCC are urgently needed. Circular RNAs (circRNAs) have been found to play a key role in the occurrence and development of HCC, while exosomes play an important role in intercellular communication; thus, the combination of circRNAs and exosomes may have inestimable potential in early diagnosis and curative therapy. Previous studies have shown that exosomes can transfer circRNAs from normal or abnormal cells to surrounding or distant cells; thereafter, circRNAs influence target cells. This review summarizes the recent progress regarding the roles of exosomal circRNAs in the diagnosis, prognosis, occurrence and development and immune checkpoint inhibitor and tyrosine kinase inhibitor resistance of HCC to provide inspiration for further research.

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“…Many studies have demonstrated that during the progression of many types of cancer such as lung, bladder, and liver cancer, tumor-associated sEVs carry and release a variety of active components such as miRNAs, proteins, and circRNAs into the surrounding cells. This further promotes the metastasis of tumor cells by causing EMT of the recipient cells through various pathways [ 24 , 48 , 49 ]. In addition, sEVs affect the EMT of recipient cells and play an important role in CRC metastasis ( Table 2 ).…”

Section: Small Extracellular Vesicles Mediate Epithelial Mesenchymal ...mentioning

confidence: 99%

The Biological Effect of Small Extracellular Vesicles on Colorectal Cancer Metastasis

Wang

Huang

et al. 2022

Cells

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Colorectal cancer (CRC) is a malignancy that seriously threatens human health, and metastasis from CRC is a major cause of death and poor prognosis for patients. Studying the potential mechanisms of small extracellular vesicles (sEVs) in tumor development may provide new options for early and effective diagnosis and treatment of CRC metastasis. In this review, we systematically describe how sEVs mediate epithelial mesenchymal transition (EMT), reconfigure the tumor microenvironment (TME), modulate the immune system, and alter vascular permeability and angiogenesis to promote CRC metastasis. We also discuss the current difficulties in studying sEVs and propose new ideas.

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Hepatic stellate cell exosome-derived circWDR25 promotes the progression of hepatocellular carcinoma <i>via</i> the miRNA-4474-3P-ALOX-15 and EMT axes

Abstract: Keywordsliver cancer, mesenchymal cells, extracellular vesicles, circular RNA, prognosisRecently, the emerging role of circular RNAs (circRNAs) in tumor development and progression

Cited by 26 publications

References 43 publications

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

Exosomes and circular RNAs: promising partners in hepatocellular carcinoma from bench to bedside

The Biological Effect of Small Extracellular Vesicles on Colorectal Cancer Metastasis

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