Autophagy
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2025
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IF 14.3
Mi Zhou,Minyu Chen,Zhousan Zheng,Qihao Li,Lican Liao,Yunfei Wang,Yi Xu,Guannan Shu,Junhang Luo,Taowei Yang,Jiaxing Zhang
The tumor microenvironment (TME) in renal cell carcinoma (RCC) frequently exhibits significant immune cell infiltration. However, tumor cells often manage to evade immune surveillance. This study revealed the mechanism by which circular RNA circGRAMD4 regulates NBR1. CircGRAMD4 is markedly elevated in RCC, and its high levels are correlated with a poor prognosis. Notably, the absence of circGRAMD4 has been demonstrated to result in a significant inhibition of renal cancer cell growth. This inhibition has been attributed to an enhanced anti-tumor immunity mediated by CD8+ T cells. Mechanistically, circGRAMD4 interacts with the RBM4 protein, stabilizing the autophagic cargo receptor NBR1 mRNA. This interaction promotes NBR1 expression, which in turn leads to the degradation of MHC-I molecules through macroautophagy/autophagy pathways. Consequently, this process affects renal cancer cell antigen presentation, induces CD8+ T cell dysfunction, and contributes to tumor immune escape. Moreover, by inhibiting circGRAMD4 and using immune checkpoint blockers (ICB), the immunosuppressive TME is altered to prevent tumor immune evasion, ultimately increasing the effectiveness of ICB treatment. The discovery highlights the significant impact of circGRAMD4 on RCC immune escape and proposes that blocking circGRAMD4 could serve as a promising immunotherapy strategy when combined with ICB to enhance patient outcomes.
研究领域:
肿瘤学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
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IF 4.872
Rili Hao,Feng Li,Xinyu Song,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li
Cadmium pollution and poisoning are serious environmental and pharmacological concerns, and effective drugs can alleviate or offset cadmium-induced toxicity are badly needed. In this study, Caffeic acid phenethyl ester (CAPE), a major active component of propolis, showed protective effect against CdCl 2 -induced toxicology by suppressing autophagy in HepG2 cells. CircRNAs are increasingly perceived as vital regulators in the process of autophagy. However, it remain unclear whether circRNAs are involved in CAPE's protection against CdCl 2 -induced autophagy. Under this context, the roles of CircRNA (hsa_circ_0040768) in CAPE's protection against CdCl 2 -induced damage were investigated by PCR and Western blot. Results showed that CAPE significantly ( P < 0.05) increased cell viability via inhibiting CdCl 2 -induced autophagy, and this process was regulated by hsa_circ_0040768/MAP1LC3B axis. Overexpressing hsa_circ_0040768 led to reduced cell viability and increased autophagy in CAPE-treated HepG2 cells exposed to CdCl 2 . In contrast, silencing hsa_circ_0040768 showed similar protective effect to CAPE. These results show for the first time the involvement of the hsa_circ_0040768/MAP1LC3B axis in the CAPE's protection against CdCl 2 -induced autophagy, and provide novel insights into the pathogenesis and potential prevention/treatment of cadmium-associated diseases.
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2020
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IF 5.186
Zhai Qiaoli,Zhao Yi,Wang Linping,Dai Yan,Zhao Peiqing,Xiang Xinxin,Liu Kui,Du Wenyan,Tian Wenxiu,Yang Baoye,Li Tao,Wang Lianqing
Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.
研究领域:
分子生物学
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骨代谢
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基因组学
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产品关联
DOI
PubMed
高影响因子
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
·
2020
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IF 2.074
AiJun Huang,LiPing Chen,YiMing Wang,ShuQiang Ma,Song Jin,Hanzhou Cai,Xingzhong Huang,Hongbo Zhang,ZengRong Wang,Kun Lin,Fangsiyu Lin
Background:5-fluorouracil (5-FU) is a widely used drug for cancer treatment, but its effect and underlying mechanisms on osteosarcoma (OS) cells remain unclear.Methods:U2OS and MG63 cells were treated with 0, 50, 100, and 500 μM 5-FU. MTS and flow cytometry were used to examine the effect of 5-FU on cell viability and apoptosis, respectively. Circular RNA (circRNA) expression was detected using RNA sequencing and quantitative real-time PCR (qPCR). Differentially expressed circRNAs were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to predict their functions. A circRNA–miRNA–mRNA interaction network was generated to analyze the regulatory networks of 5-FU–induced differentially expressed circRNAs. Western blotting (WB) was used to verify the protein in the downstream of circRNAs.Results:5-FU inhibited the cell viability of the MG63 cells in a concentration-dependent manner. The most significant effect was observed in the cells treated with 500 μM 5-FU. Apoptosis was also increased in the MG63 cells after 500 μM 5-FU treatment for 3 days. RNA sequencing results showed that 183 differentially expressed circRNAs (172 upregulated and 11 downregulated) in 5-FU–treated cells. KEGG and GO analysis showed that the differentially expressed circRNAs were primarily enriched in proliferation-, apoptosis-, and metabolism-related functions. qPCR was used to verify the most upregulated and downregulated circRNAs. The circRNA–miRNA–mRNA interaction network showed that these 8 circRNAs had a sizable regulatory network that links a series of genes involved in tumor suppression.Conclusion:5-FU treatment resulted in the differentially expressed circRNAs that were proliferation- and apoptosis-associated and were involved in the 5-FU–induced inhibition of tumor proliferation in OS cells.
研究领域:
肿瘤学
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分子生物学
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基因组学
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癌症治疗
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DOI
PubMed
高影响因子
Cancer Cell International
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2021
·Vol. 21
·期 1
·1-13
·
IF 5.722
Zheng Kebin,Xie Haipeng,Wu Wensong,Wen Xichao,Zeng Zhaomu,Shi Yanfang
Background Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma.Methods Firstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR.Results The results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3′-untranslated region (UTR) of TCF12.Conclusion sOverall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
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IF 6.7
Chunhan Li,Yuanhang Wei,Xinwei Li,Peng Jiang,Xuran Dong,Qunqun Guo,Qingguo Xu,Xiyue Cao,Jianfei Xia,Zonghua Wang
Circular RNA (circRNA), a covalently closed RNA molecule, has demonstrated significant potential as a new emerging biomarker in the field of liquid biopsy due to its unique stability, tissue-specific expression patterns, and dysregulated expression in various diseases. However, the accurate quantification of circRNAs is still a tough problem because of homologous linear RNA influence, low-expression abundance, and concomitant interference in blood. Therefore, in this study, a nanobiosensor integrated with catalytic hairpin assembly (CHA) cascade amplification and magnetic control depuration, which can analyze circRNA expressed in human tissue and blood, was reported. The CHA cascade amplification is achieved by coupling the CHA reaction with subsequent formation of G-quadruplex-hemin DNAzymes, resulting in a remarkable enhancement in specificity and sensitivity. The robustness of the nanobiosensor in tissue and blood samples is supported by magnetic-driven transfer of oligonucleotide probes from the complex biological matrix after target recognition. As a proof of concept, the nanobiosensor was designed and fabricated to detect cSMARCA5, a kind of circRNA highly associated with the occurrence of hepatocellular carcinoma. The nanobiosensor exhibits a broad linear range from 10 fM to 100 nM, with a detection limit as low as 1.93 fM. Furthermore, in clinical validation experiments, the nanobiosensor successfully reveals the expression levels of cSMARCA5 in liver tissue and whole blood samples, from which hepatocellular carcinoma patients are accurately screened out among normal people, thereby providing a highly promising circulating RNA-based liquid biopsy tool with significant potential for clinical application.
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2022
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IF 6.832
Chun Chen,Xiaolong Chang,Shifei Zhang,Qi Zhao,Chunyan Lei
Emerging studies show that circRNA catenin beta 1 (circCTNNB1) plays a critical role in cancer. However, the expression and function of circCTNNB1 in cerebral ischemia/reperfusion injury (IRI) have not been reported. The present study discovered that circCTNNB1 and scavenger receptor class B type 1 (SRB1) expression levels were significantly down-regulated in mouse astrocytes (mAS) treated with oxygen glucose deprivation and reperfusion (OGD/R), and similar results were observed in a mouse middle cerebral artery occlusion model. Overexpression of circCTNNB1 alleviated cell apoptosis, oxidative stress and the inflammatory response induced by OGD/R in vitro. Up-regulation of circCTNNB1 increased SRB1 expression levels to protect mAS cells from OGD/R-induced damage. CircCTNNB1 and SRB1 interacted with miR-96-5p, and the overexpression of miR-96-5p efficiently reversed the function of circCTNNB1 in OGD/R-treated mAS cells. CircCTNNB1 protected against cerebral ischemia-reperfusion injury by up-regulating SRB1 in vivo. In conclusion, our findings suggest that circCTNNB1 acts as a competitive endogenous RNA for miR-96-5p to alleviate cerebral IRI, which provides novel evidence that circCTNNB1 and SRB1 may be biomarkers and therapeutic targets for cerebral IRI.
研究领域:
神经科学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2026
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IF 11.8
Lingsong Lu,Yingying Zhang,Bei Liu,Nuo zhou,Dao jun Yu,Ying Wang
Circular RNAs (circRNAs) represent an emerging family of noncoding transcripts defined by closed-loop architecture, which are now established as key participants in the etiology of tumorigenesis and malignant progression. While circRNAs show potential as therapeutic targets and biomarkers, the accurate detection of circRNAs remains challenging due to interference from homologous linear RNAs. In this study, an ultrasensitive method for detecting circ_0051240 based on the sulfhydrated toehold capture probe-initiator assembly-mediated hybridization chain reaction (HCR) and the CRISPR-Cas12a system was developed. The capture probe (with a toehold domain)-initiator strand duplex was ingeniously fabricated to identify the back-splice junction (BSJ) of circRNA. After magnetic enrichment and separation by the Fe 3 O 4 -Au@UIO-66-NH 2 nanocomposite, the initiator strand (H0) was delivered to trigger HCR. The HCR product dsDNA concatemers contained multiply repeated CRISPR-targetable DNA sites that were readily recognized by the CRISPR RNA (crRNA). This specific recognition and binding activated the CRISPR-Cas12a system's collateral endonuclease activity, leading to cleavage of the fluorophore-quencher (FQ) reporters and fluorescence emission at a characteristic wavelength. This design eliminated linear RNA-related interference and enhanced the detection of fluorescence intensity (FI). Under optimal conditions, the proposed HCR/CRISPR-Cas12a method exhibited a wide quantitative measurement range spanning from 45 pM up to 180 nM, achieving a notable limit of detection (LOD) of 0.03 pM. In this study, a novel circRNA sensing strategy capable of accurate and highly sensitive quantification of ovarian cancer-specific circRNA was reported. The proposed method exhibits acceptable performance when compared to present approaches.
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产品关联
DOI
PubMed
高影响因子
Toxicology Research
·
2021
·Vol. 10
·期 5
·1013-1021
·
IF 3.524
Liu Yan-ping,Cai Ying,Lei Yuan-di,Yuan Xiao-yan,Wang Ye,Yi Shan,Li Xun-ya,Huang Lian,Long Ding-xin,Zhang Zhao-hui
Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK–STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.
研究领域:
分子生物学
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毒理学
·
生物信息学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）