INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2024
·Vol. 25
·期 5
·2817
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IF 4.9
Gengchen Xie,Bo Lei,Zhijie Yin,Fei Xu,Xinghua Liu
Our previous study has reported that metastasis-associated protein 2 (MTA2) plays essential roles in tumorigenesis and aggressiveness of gastric cancer (GC). However, the underlying molecular mechanisms ofMTA2-mediated GC and its upstream regulation mechanism remain elusive. In this study, we identified a novel circular RNA (circRNA) generated from theMTA2gene (circMTA2) as a crucial regulator in GC progression. CircMTA2was highly expressed in GC tissues and cell lines, and circMTA2promoted the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circMTA2interacted with ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) to restrainMTA2ubiquitination and stabilizeMTA2protein expression, thereby facilitating tumor progression. Moreover, circMTA2was mainly encapsulated and transported by exosomes to promote GC cell progression. Taken together, these findings uncover that circMTA2suppressesMTA2degradation by interacting with UCHL3, thereby promoting GC progression. In conclusion, we identified a cancer-promoting axis (circMTA2/UCHL3/MTA2) in GC progression, which paves the way for us to design and synthesize targeted inhibitors as well as combination therapies.Keywords:CircRNAs;MTA2;gastric cancer;UCHL3;ubiquitination
研究领域:
分子生物学
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肿瘤学
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细胞生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Wu Zhiwei,Zhang Fan,Yang Kai,He Wenfei
Breast cancer is the leading cause of cancer-related death in women worldwide, and its developmental mechanisms involve complex factors. Recent studies have shown that ferroptosis is closely related to the occurrence and progression of breast cancer. However, the role of circular RNAs (circRNAs) in regulating ferroptosis in breast cancer remains unclear. In this study, we investigated the regulatory role of circSCD1 (hsa_circ_0019512) in breast cancer. We examined the expression of circSCD1 in breast cancer cell lines and explored its impact on cell viability and colony formation. We also evaluated the involvement of circSCD1 in ferroptosis by measuring the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and intracellular iron. In vivo xenograft experiments were performed to confirm the role of circSCD1 in promoting tumor growth and inhibiting ferroptosis.Furthermore, we investigated the mechanism by which circSCD1 regulates SCD1 protein stability through ubiquitination and identified the interaction between circSCD1 and the deubiquitinase OTUB1. Our results showed that circSCD1 was upregulated in breast cancer cell lines and promoted cell viability and colony formation. Knockdown of circSCD1 increased MDA and ROS levels, decreased GSH levels, and enhanced ferroptosis in breast cancer cells. In vivo, circSCD1 knockdown significantly reduced tumor size and weight, while its overexpression enhanced tumor growth. Mechanistically, circSCD1 interacted with OTUB1 to inhibit the ubiquitination and degradation of SCD1 protein, thereby stabilizing its expression. Rescue experiments demonstrated that SCD1 overexpression partially reversed the effects of circSCD1 knockdown on cell proliferation and ferroptosis. Our findings suggest that circSCD1 plays a crucial role in promoting breast cancer cell growth and inhibiting ferroptosis by regulating SCD1 protein stability. Targeting the circSCD1/OTUB1/SCD1 axis may provide a potential therapeutic strategy for breast cancer treatment.
研究领域:
肿瘤学
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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
Molecular Medicine Reports
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2015
·Vol. 12
·期 5
·6656-6662
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IF 1.554
Chengfei Zheng,Hui Niu,Ming Li,Hongkun Zhang,Zhenggang Yang,Lu Tian,Ziheng Wu,Donglin Li,Xudong Chen
Aortic aneurysm is a cardiovascular condition with a serious risk of mortality and the dismal prognosis of any type of major cardiovascular disease. The present study found that tissues from aortic aneurysm patients and hypoxic aortic smooth muscle cells showed aberrant high expression of the cyclic RNA hsa‑circ‑000595, as demonstrated by polymerase chain reaction array screening. Knockdown of hsa‑circ‑000595 resulted in a decreased apoptotic rate of human aortic smooth muscle cells. Furthermore, it was determined that miR‑19a is a target of hsa‑circ‑000595. The results of the present study laid an epigenetic foundation for exploring the underlying mechanisms of the development of aortic aneurysm.
研究领域:
心血管疾病
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
iScience
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2023
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IF 5.8
Shuai Chen,Peng Song,Yu Wang,Zeng Wang,Jiaming Xue,Yicheng Jiang,Yan Zhou,Jie Zhao,Liming Tang
Circular RNA (circRNA) is a special category of non-coding RNA that has garnered increasing attention in the exploration of lipid metabolism. However, the functional regulation mechanisms of circRNAs in obesity diseases remain unclear. By whole transcriptome sequencing, a total of 164 circular RNAs were found to exhibit differential expression between lean and obese individuals. RT-qPCR was used to detect significant expression of circMAPK9 in obese individuals, and it was closely related to BMI. Western blot, triglyceride detection, and Oil Red O staining were employed to investigate the role of circMAPK9/hsa-miR-1322/FTO in adipogenesis. In adipocytes, the connection between hsa-miR-1322 and circMAPK9 was verified using fluorescence in situ hybridization, luciferase reporter assay, and RNA immunoprecipitation. It was found that circMAPK9 competed for binding hsa-miR-1322 in the cytoplasm, weakening the inhibitory effect on FTO and promoting adipogenesis. Our study revealed the regulatory mechanism and important role of circMAPK9 in the process of adipogenesis.
研究领域:
分子生物学
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基因组学
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代谢
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
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2025
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IF 3.7
Qiuyun Wu,Qianyi Zhang,Chunmeng Jin,Xue Liu,Hongmin Yu
Background Silicosis, one of the serious occupational diseases, is mainly manifested by pulmonary fibrosis induced by long-term exposure to silica particles in workplace. Evidence demonstrates that circular RNAs (circRNAs) are interesting regulators of pulmonary fibrosis process. So, further elucidation of the role of circRNAs may provide a new perspective into mechanisms driving pulmonary fibrosis and silicosis. Methods The characteristics of circRNA homer scaffold protein 1 (hsa_circ_0006916, circHOMER1) was assessed using Actinomycin D, RNase R, and nucleoplasmic separation assay. The histopathological examination and Enzyme-linked immunosorbent assay (ELISA) were used to confirm circHOMER1 function in mouse lung tissues under silica particle exposure. The expression of circHOMER1, human antigen R (HuR) and NADPH oxidase 4 (NOX4) was identified by western blot or RT-qPCR assay. The RNA immunoprecipitation (RIP) assay and plasmid co-transfection were used to analyze the interaction between circHOMER1, HuR and NOX4. Results We confirmed an upregulated circHOMER1 in silicosis fibrosis. Functional assays showed that the knockdown of circHOMER1 suppressed the viability of fibroblasts and the production of fibrotic molecules and alleviated the histology fibrotic changes in lung tissues from mouse exposed to silica particles. Mechanistically, we found that circHOMER1 directly bound to HuR and promoted its protein expression in fibroblasts. And, circHOMER1 further regulated HuR/NOX4 signaling axis through HuR to stabilize NOX4 mRNA, which enhanced the production of reactive oxygen species (ROS), thereby promoting the silicosis fibrosis process. Conclusion This study revealed the role of circHOMER1 in silica-induced pulmonary fibrosis, suggesting that the inhibition of circHOMER1 may be a potential therapeutic approach to relieve the pathological process of silicosis.
研究领域:
分子生物学
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肺病学
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职业医学
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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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DOI
PubMed
高影响因子
ANTI-CANCER DRUGS
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2021
·Vol. 33
·期 1
·e145
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IF 2.248
Liu Dan,Wang Yaya,Li Haiming,Peng Sida,Tan Huo,Huang Zhenqian
Multiple myeloma is a frequent hematologic malignancy. Bortezomib is the first-line drug for multiple myeloma chemotherapy. The present study aimed to investigate the potential role and mechanism of circular RNA chaperonin containing TCP1 subunit 3 (circ-CCT3) in bortezomib resistance of multiple myeloma . The levels of circ-CCT3, microRNA-223-3p ( miR-223-3p ), and bromodomain-containing 4 (BRD4) were detected by quantitative real-time PCR or western blot. Cell Counting Kit-8 (CCK-8) method was used to measure the half-inhibitory concentration of bortezomib and cell viability. Cell cycle distribution, apoptosis, proliferation and migration were determined by flow cytometry, 5-ethynyl-2′-deoxyuridine, and wound healing assay. The levels of relevant proteins were checked via western blot. The binding association between miR-223-3p and circ-CCT3/BRD4 was validated via a dual-luciferase reporter assay. Circ-CCT3 and BRD4 were upregulated, while miR-223-3p was downregulated in bortezomib -resistant multiple myeloma patients and cells. Silencing of circ-CCT3 enhanced the sensitivity of bortezomib -resistant multiple myeloma cells to bortezomib . Circ-CCT3 knockdown weakened bortezomib resistance via modulating miR-223-3p . Moreover, miR-223-3p increased bortezomib sensitivity by inhibiting BRD4. Downregulation of circ-CCT3 attenuated bortezomib resistance of multiple myeloma via regulating miR-223-3p /BRD4 pathway, which provided a new potential target for multiple myeloma chemoresistance.
研究领域:
肿瘤学
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分子生物学
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血液学
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DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Jiankun Zang,Yousheng Wu,Xuanlin Su,Kaiwei Cai,Man Ke,Niu He,Huili Zhu,Zefeng Tan,Jielin Zhu,Wensheng He,Min Peng,Shiqing Zhang,Hongcheng Mai,Anding Xu,Dan Lu
Small extracellular vesicles (sEVs) contain abundant circular RNAs (circRNAs) and are involved in cellular processes, particularly hypoxia. However, the process that packaging of circRNAs into neuronal sEVs under hypoxia is unclear. This study revealed the spatial mechanism of the Fused in Sarcoma protein (FUS) that facilitates the loading of functional circRNAs into sEVs in hypoxia neurons. It is found that FUS translocated from the nucleus to the cytoplasm and is more enriched in hypoxic neuronal sEVs than in normal sEVs. Cytoplasmic FUS formed aggregates with the sEVs marker protein CD63 in cytoplasmic stress granules (SGs) under hypoxic stress. Meanwhile, cytoplasmic FUS recruited of functional cytoplasmic circRNAs to SGs. Upon relief of hypoxic stress and degradation of SGs, cytoplasmic FUS is transported with those circRNAs from SGs to sEVs. Validation of FUS knockout dramatically reduced the recruitment of circRNAs from SGs and led to low circRNA loading in sEVs, which is also confirmed by the accumulation of circRNAs in the cytoplasm. Furthermore, it is showed that the FUS Zf_RanBP domain regulates the transport of circRNAs to sEVs by interacting with hypoxic circRNAs in SGs. Overall, these findings have revealed a FUS-mediated transport mechanism of hypoxia-related cytoplasmic circRNAs loaded into sEVs under hypoxic conditions.
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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PubMed
高影响因子
Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-19
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IF 6.1
Xu Haotian,Zheng Yue,Wu Jiaxi,Zhang Ruirui,Zhao Qingyun,Chen Sixian,Peng Wenyi,Cai Dunyu,Gao Yihong,Chen Xingcai,Li Deqing,yuan Shengyi,Li Gang,Nan Aruo
Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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基因组学
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DOI
PubMed
高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-15
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IF 14.7
Zhou Zhixin,Han Bing,Wang Yu,Lin Nina,Zhou Zhongqiu,Zhang Yuan,Bai Ying,Shen Ling,Shen Yanfei,Zhang Yuanjian,Yao Honghong
While circular RNAs (circRNAs) exhibit lower abundance compared to corresponding linear RNAs, they demonstrate potent biological functions. Nevertheless, challenges arise from the low concentration and distinctive structural features of circRNAs, rendering existing methods operationally intricate and less sensitive. Here, we engineer an intelligent tetrahedral DNA framework (TDF) possessing precise spatial pattern-recognition properties with exceptional sensing speed and sensitivity for circRNAs. The signal output of TDF sensor occurs only when multivalent spatial pattern-recognition of a circRNA in unamplified samples. Using this sensor, we visualize the real-time response of endogenous circRNA expression in vitro neuronal cells and in vivo brain between pre-stroke and post-stroke male mice, identify the patients with acute ischemic stroke in clinical samples, as well as track the delivery of circRNA in photochromic stroked animal model. Thus, the TDF sensor provides a fast and sensitive tool for the detection of circRNA abundance in both physiological and pathophysiological conditions.
研究领域:
分子生物学
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生物医学工程
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神经科学
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DOI
PubMed
高影响因子
CANCER GENE THERAPY
·
2021
·Vol. 29
·期 1
·101-121
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IF 5.987
Pan Jiongwei,Huang Gang,Yin Zhangyong,Cai Xiaoping,Gong Enhui,Li Yuling,Xu Cunlai,Ye Zaiting,Cao Zhuo,Cheng Wei
Significantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 4
·e24347
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IF 3.124
Shan Chen,Kelin Hong,Long Zhou,Ruizhi Ran,Jinqi Huang,Yong Zheng,Maohui Xing,Yanli Cai
Background CircRNA is a very important functional RNA that plays an important role in the development and metabolism of cancer. However, the study of circRNA in NSCLC has not been fully elucidated. Methods The expression of hsa_circ_0017620, SFMBT2, miR-520a-5p, and KRT5 was determined using qRT-PCR. KRT5, Twist1, E-cadherin, and Ki67 protein expression were measured with western blot. The positive expression rates of Ki67 and Vimentin were determined by immunohistochemistry assay. 5-Ethynyl-2’-deoxyuridine (EdU), colony formation, and MTT assays were used to assess cell proliferation. Transwell migration and invasion assay were applied to determine cell migration and invasion. Dual-luciferase reporter and RNA immunoprecipitation assays were used to verify the relationship among hsa_circ_0017620, miR-520a-5p, and KRT5. The animal experiment was used to ensure the effects of hsa_circ_0017620 on tumor growth in vivo . Results Hsa_circ_0017620 was upregulated in NSCLC cells and tissues. MiR-520a-5p had been verified to be a target miRNA of hsa_circ_0017620 and KRT5 had been verified to be a target mRNA of miR-520a-5p in NSCLC cells. Knockdown of hsa_circ_0017620 inhibited cell proliferation, migration, and invasion in NSCLC cells, which was reversed by downregulating miR-520a-5p or upregulating KRT5 in NSCLC. Overexpression of hsa_circ_0017620 had opposite effects in NSCLC. Moreover, hsa_circ_0017620 silencing inhibited tumor growth in vivo of NSCLC. Conclusion In this study, we found that hsa_circ_0017620 played an important role in NSCLC progression. Hsa_circ_0017620 regulated cell proliferation, invasion, and migration through targeting miR-520a-5p/KRT5 axis in NSCLC, providing a potential new target for the treatment and diagnosis of NSCLC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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