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XIA LIANGJIANG, LI GUANGBIN, ZHOU QINGWU, FENG YU, MA HAITAO. CircRNA circ_0015278 induces ferroptosis in lung adenocarcinoma through the miR-1228/P53 axis. Oncol Res 2025; 33:465-475. [PMID: 39866239 PMCID: PMC11753987 DOI: 10.32604/or.2024.050835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 05/11/2024] [Indexed: 01/28/2025] Open
Abstract
Background Circular RNAs play an important role in regulating lung adenocarcinoma (LUAD). Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD. However, the biological mechanism of circ_0015278 in LUAD has not been fully clarified, especially in ferroptosis. Materials and Methods Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278, subsequently confirmed by luciferase reporter assays. The impact of Circ_0015278 on cell proliferation, migration, invasion, and ferroptosis was investigated through a loss-of-function experiment. A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth. Results Circ_0015278 exhibited downregulation in LUAD. It inhibited cell proliferation, migration, and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism. Moreover, circ_0015278 suppressed tumour growth in mice. Conclusions Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD. Furthermore, it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.
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Affiliation(s)
- LIANGJIANG XIA
- Department of Thoracic Surgery, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - GUANGBIN LI
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - QINGWU ZHOU
- The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - YU FENG
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - HAITAO MA
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
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Si T, Huang L, Liang T, Huang P, Zhang H, Zhang M, Zhou X. Ruangan Lidan decoction inhibits the growth and metastasis of liver cancer by downregulating miR-9-5p and upregulating PDK4. Cancer Biol Ther 2023; 24:2246198. [PMID: 37773732 PMCID: PMC10543352 DOI: 10.1080/15384047.2023.2246198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/04/2023] [Indexed: 10/01/2023] Open
Abstract
A growing number of studies have suggested that traditional Chinese medicine (TCM) plays an essential role in the development and occurrence of liver cancer. However, the function of Ruangan Lidan decoction (RLD) in liver cancer are not yet adequately identified and manifested, which attracted our attention. The key genes related to liver cancer and RLD and the upstream miRNAs of PDK4 were obtained based on bioinformatics analysis, followed by verification of the targeting relationship between miR-9-5p and PDK4. Next, Huh7 cells were treated with RLD to detect cell proliferation, colony formation, migration, invasion, and apoptosis by multiple assays with gain- and loss-of-function experiments. Moreover, subcutaneous transplanted tumor model and lung metastasis model of liver cancer in nude mice were established to further verify the functional role of RLD in liver cancer growth and metastasis via miR-9-5p/PDK4 axis. Bioinformatics analysis found that PDK4 and miR-9-5p were related to liver cancer, and PDK4 may be a downstream regulator of RLD. miR-9-5p could target and inhibit PDK4. In vitro cell experiments demonstrated that RLD suppressed liver cancer cell proliferation, invasion and migration, and promoted apoptosis by inhibiting miR-9-5p expression and promoting PDK4 expression. In vivo animal experiments further confirmed that RLD inhibited liver cancer growth and metastasis via upregulation of miR-9-5p-dependent PDK4. RLD downregulated miR-9-5p and upregulated PDK4 to inhibit the proliferation, migration, invasion, and induce apoptosis, thereby suppressing the growth and metastasis of liver cancer, highlighting a potential novel target for treatment of liver cancer.
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Affiliation(s)
- Tao Si
- Department of Oncology, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, China
| | - Liyin Huang
- Graduate school, Guangxi University of Chinese Medicine, Nanning, China
| | - Ting Liang
- Graduate school, Guangxi University of Chinese Medicine, Nanning, China
| | - Ping Huang
- Department of Oncology, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, China
| | - Hongyu Zhang
- Department of Clinical Laboratory, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, China
| | - Mingmin Zhang
- Department of Oncology, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, China
| | - Xiaoling Zhou
- Department of Gastroenterology, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, China
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Chen X, Xu Y, Zhou Z, Zhao P, Zhou Z, Wang F, Zhong F, Du H. CircUSP10 promotes liver cancer progression by regulating miR-211-5p/TCF12/EMT signaling pathway. Heliyon 2023; 9:e20649. [PMID: 37829805 PMCID: PMC10565698 DOI: 10.1016/j.heliyon.2023.e20649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 09/22/2023] [Accepted: 10/03/2023] [Indexed: 10/14/2023] Open
Abstract
There is no precise diagnosis or prognosis for liver cancer (LC) using a single biomarker. Circular RNAs (circRNAs) contribute to the pathogenesis of different cancers, but their role in LC is not entirely understood. In this study, circUSP10, an aberrantly expressed circRNA in LC, was screened using the Gene Expression Omnibus database, and its tissue-specific expression was verified using qRT-PCR. In vitro, functional assays and nude mouse tumorigenesis models were used to investigate circUSP10 role in LC. RNA immunoprecipitation and dual-luciferase reporter assays were performed to study the mechanistic relationship between circUSP10, miR-211-5p, and transcription factor 12 (TCF12). We found that circUSP10 expression was upregulated in LC tissues and cells. CircUSP10 expression was linked to tumor size and tumor node metastasis stage and negatively correlated with LC prognosis. In vitro assays confirmed circUSP10-mediated proliferation, migration, and invasion of LC cells and their association with the epithelial-mesenchymal transition (EMT) pathway. Mechanistically, circUSP10 adsorbed miR-211-5p, which regulated TCF12 and promoted tumorigenesis via the EMT signaling pathway. Therefore, our results suggest that circUSP10 may promote LC progression by modulating the miR-211-5p/TCF12/EMT signaling cascade and may serve as a potential biomarker for LC diagnosis and prognosis.
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Affiliation(s)
- Xiang Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- Department of Laboratory Medicine, Nantong First People's Hospital and The Second Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China
| | - Yao Xu
- Department of Laboratory Medicine, Nantong First People's Hospital and The Second Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China
| | - Zhengyang Zhou
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Ping Zhao
- Department of Laboratory Medicine, Nantong First People's Hospital and The Second Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China
| | - Zhou Zhou
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China
| | - Feng Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China
| | - Fengyun Zhong
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Hong Du
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
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Zhou C, Zhu D, Zhou S, Wang H, Huang M. Screening differential circular RNA expression profiles and the potential role of hsa_circ_0085465 in liver cancer. J Cancer Res Ther 2023; 19:548-555. [PMID: 37470573 DOI: 10.4103/jcrt.jcrt_1868_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
Aims This study aimed to screen the circular RNAs (circRNAs) that are differentially expressed between liver cancer and paired paracarcinoma tissues and then elucidate their role in cancer progression. Materials and Methods High-throughput sequencing of cancer and paired paracarcinoma tissues was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the parental genes of the differentially expressed circRNAs, which were also verified via real-time quantitative polymerase chain reaction analysis of the tissues. In addition, the function of selected circRNAs was determined using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium (MTS) and transwell assays. Results Total 218 and 121 circRNAs were differentially upregulated and downregulated, respectively; these were mainly enriched with GO and KEGG terms related to biological functions. From five representatives of the differentially expressed circRNAs, we selected hsa_circ_0085465 for further analysis, discovering that its overexpression promoted the proliferation, migration, and invasion of 97 L cells. Conclusion Taken together, our results suggest that hsa_circ_0085465 is relevant to liver cancer progression.
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Affiliation(s)
- Churen Zhou
- Department of Interventional Radiology Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Duo Zhu
- Department of Interventional Radiology Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sibin Zhou
- Department of Interventional Radiology Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Haofan Wang
- Department of Interventional Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Mingsheng Huang
- Department of Interventional Radiology Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Liu C, Huang R, Yu H, Gong Y, Wu P, Feng Q, Li X. Fuzheng Xiaozheng prescription exerts anti-hepatocellular carcinoma effects by improving lipid and glucose metabolisms via regulating circRNA-miRNA-mRNA networks. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 103:154226. [PMID: 35689900 DOI: 10.1016/j.phymed.2022.154226] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 05/22/2022] [Accepted: 05/31/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major threat to human health due to its high lethality. Our previous studies suggested that Fuzheng Xiaozheng prescription (FZXZP), an effective Chinese medicine, demonstrated significant suppressive effects on HCC. However, its underlying mechanism remains largely unclear. PURPOSE This study aimed to investigate the anti-HCC mechanisms of FZXZP from transcriptomic sequencing based on a holistic perspective. METHODS Rat HCC model was induced by diethylnitrosamine, and then the model was administered with two doses of FZXZP, high and low. Sodium demethylcantharidate was used as a positive control. Subsequently, microarrays of circRNA, miRNA and mRNA were performed on the blank, model, high and low dose groups, respectively, and the competitive binding mechanisms among them were further analyzed by bioinformatics. Then, the circRNA-miRNA-mRNA networks were constructed to mine the targeted-RNAs of FZXZP in HCC, as well as to explore their potential regulatory mechanisms. Finally, functions and pathways of the FZXZP targeted genes in rat HCC were annotated with GO and KEGG, and qRT-PCR was performed to validate the accuracy of the above analyses in this study. RESULTS The results showed that FZXZP significantly inhibited the development and progression of HCC in rats, improved the pathological conditions and suppressed the proliferation of HCC cells. Subsequently, after a series of screening, the competing endogenous RNA networks (circRNA-miRNA-mRNA), consisting of 2 circRNAs, 7 miRNAs and 104 mRNAs, were finally established. KEGG and GO analyses of the networks revealed that lipid metabolism related pathways, such as fatty acid metabolism, bile secretion and PPAR pathway, were significantly enriched. In the further hubgene network analysis, in addition to lipid metabolism, aberrant glucose metabolism was found to be ameliorated by G6pc and Pklr in hubgenes. Finally, the qRT-PCR analyses confirmed that the expression tendencies of the above targeted genes were correct and believable in transcriptomic sequencings, and qRT-PCR results of the genes closely related to proliferation, invasion and apoptosis of HCC also indicated the inhibitory effects of FZXZP on HCC obviously. CONCLUSION FZXZP demonstrated significant anti-HCC effects through improving lipid and glucose metabolism, restoring the metabolic homeostasis of the liver via circRNA-miRNA-mRNA networks.
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Affiliation(s)
- Chao Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Renwei Huang
- Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources, College of Chemistry and Life Sciences, Chengdu Normal University, Chengdu, 611130, China
| | - Han Yu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yanju Gong
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Peijie Wu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Quansheng Feng
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xia Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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CircFMN2 Boosts Sorafenib Resistance in Hepatocellular Carcinoma Cells via Upregulating CNBP by Restraining Ubiquitination. JOURNAL OF ONCOLOGY 2022; 2022:2674163. [PMID: 35909906 PMCID: PMC9334069 DOI: 10.1155/2022/2674163] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/25/2022] [Accepted: 06/29/2022] [Indexed: 12/11/2022]
Abstract
Purpose Noncoding RNAs exert critical biological effects in hepatocellular carcinoma (HCC). The role of circFMN2, a newly discovered functional RNA in prostate cancer and colorectal cancer, was investigated for the first time in sorafenib-resistance HCC cells. Methods The level of circFMN2 was assessed via quantitative real-time PCR (qRT-PCR). Cell proliferation was detected via CCK-8 and colony formation assay. Cell apoptosis was measured via the TUNEL assay and flow cytometry analysis. A Western blot assay was conducted to detect the CCHC-type zinc finger nucleic acid binding protein (CNBP) level and ubiquitination. RNA pull-down assay and RNA immunoprecipitation were carried out to explore the interaction between circFMN2 and CNBP. Results CircFMN2 was highly expressed in multidrug-resistant (MDR) cells. CircFMN2 overexpression exerted pro-proliferation effects in sorafenib-treated HCC cells, while depletion of circFMN2 displayed negative effect on sorafenib-treated MDR cells. Moreover, CNBP was verified as the binding protein of circFMN2. CNBP was upregulated in MDR cells, which was achieved by inhibition of ubiquitination by circFMN2. Besides, CNBP overexpression was found to boost sorafenib resistance in HCC cells. Conclusions CircFMN2 is aberrantly expressed in sorafenib-resistant HCC cells and contributes to sorafenib resistance in HCC cells via upregulation of CNBP by restraining ubiquitination.
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Niu ZS, Wang WH. Circular RNAs in hepatocellular carcinoma: Recent advances. World J Gastrointest Oncol 2022; 14:1067-1085. [PMID: 35949213 PMCID: PMC9244981 DOI: 10.4251/wjgo.v14.i6.1067] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/22/2021] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.
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Affiliation(s)
- Zhao-Shan Niu
- Laboratory of Micromorphology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Wen-Hong Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
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Circ_100395 impedes malignancy and glycolysis in papillary thyroid cancer: involvement of PI3K/AKT/mTOR signaling pathway. Immunol Lett 2022; 246:10-17. [DOI: 10.1016/j.imlet.2022.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 04/02/2022] [Accepted: 04/16/2022] [Indexed: 11/23/2022]
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Li H, Yin H, Yan Y. Circ_0041732 regulates tumor properties of triple-negative breast cancer cells by the miR-149-5p/FGF5 pathway. Int J Biol Markers 2022; 37:178-190. [PMID: 35341378 DOI: 10.1177/03936155221086599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Triple-negative breast cancer (TNBC) is a subtype of breast cancers with a high recurrence and mortality. The important factors promoting the TNBC process have not been fully identified. In this research, the role of a TNBC-related circular RNA (circRNA), circ_0041732, was revealed in TNBC cell tumor properties. METHODS The expression levels of circ_0041732, microRNA-149-5p (miR-149-5p) and fibroblast growth factor 5 (FGF5) were detected by quantitative real-time polymerase chain reaction. The protein expression was determined by Western blot analysis or immunohistochemistry assay. Cell proliferation was detected by cell counting kit-8 and cell colony formation assays. Cell apoptosis was analyzed by flow cytometry and caspase-3 activity assays. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. Cell angiogenic capacity was investigated by a tube formation assay. The targeting relationship between miR-149-5p and circ_0041732 or FGF5 was identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of circ_0041732 knockdown on tumor formation were determined by an in vivo assay. RESULTS Circ_0041732 and FGF5 expression were significantly upregulated, whereas miR-149-5p was downregulated in TNBC tissues and cells compared with normal breast tissues and cells, respectively. Circ_0041732 silencing inhibited TNBC cell proliferation, migration, invasion, and tube formation, but induced apoptosis. Additionally, circ_0041732 regulated TNBC cell tumor properties by binding to miR-149-5p. MiR-149-5p also modulated TNBC cell tumor properties by targeting FGF5. Furthermore, circ_0041732 knockdown hindered tumor formation in vivo. CONCLUSION Circ_0041732 silencing suppressed TNBC cell tumor properties by decreasing FGF5 expression through miR-149-5p. This finding demonstrated that circ_0041732 had the potential as a therapeutic target for TNBC.
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Affiliation(s)
- Hongyang Li
- Department of Internal Medicine Oncology, Lianshui People's Hospital, Lianshui City, Jiangsu Province, China
| | - Hailin Yin
- Department of Internal Medicine Oncology, Lianshui People's Hospital, Lianshui City, Jiangsu Province, China
| | - Yao Yan
- Department of Internal Medicine Oncology, Lianshui People's Hospital, Lianshui City, Jiangsu Province, China
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Zhang HZ, Zhang XD, Huang JX. Circ_0000212 affects proliferation, migration, invasion, apoptosis, and paclitaxel sensitivity of liver cancer cells by targeting miR-139-5p. Shijie Huaren Xiaohua Zazhi 2021; 29:1276-1285. [DOI: 10.11569/wcjd.v29.i22.1276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Circ_0000212 is a newly discovered non-coding RNA whose high expression promotes the progression of colorectal cancer. However, the expression patterns and roles of circ_0000212 in liver cancer remain unknown.
AIM To investigate the effect of circ_0000212 targeting miR-139-5p on cell proliferation, migration, invasion, apoptosis, and paclitaxel sensitivity in liver cancer.
METHODS RT-qPCR was applied to detect the expression of circ_0000212 and miR-139-5p in liver cancer tissues and adjacent tissues. Pearson correlation analysis was performed to determine the relationship between circ_0000212 and miR-139-5p expression in liver cancer tissues. Dual luciferase reporter assay was used to verify the targeting relationship between circ_0000212 and miR-139-5p. Liver cancer HCC9204 cells were divided into a control group, circ_0000212 interference group, circ_0000212 interference + miR-139-5p inhibitor group, paclitaxel group, paclitaxel + circ_0000212 interference group, and paclitaxel + circ_0000212 interference + miR-139-5p inhibitor group. The rate of inhibited HCC9204 cells was detected using CCK-8 method; the number of clones formed by HCC9204 cells was calculated using colony formation assay; the apoptotic rate of HCC9204 cells was evaluated by flow cytometry; and the migration and invasion of HCC9204 cells were detected by Transwell assay.
RESULTS Compared with adjacent tissue, the expression level of circ_0000212 in liver cancer tissue was significantly increased (P < 0.05), while the expression level of miR-139-5p was significantly decreased (P < 0.05). There was a negative correlation between the expression of circ_0000212 and miR-139-5p in liver cancer tissues. Circ_0000212 directly interacted with miR-139-5p. Compared with the control group, circ_0000212 expression in HCC9204 cells in the paclitaxel group was significantly reduced (P < 0.05), while miR-139-5p expression was significantly increased (P < 0.05). Compared with the control group, the numbers of clones formed and migrating and invading HCC9204 cells in the interference circ_0000212 group and paclitaxel group were significantly reduced (P < 0.05), and the inhibition rate and apoptosis rate were significantly increased (P < 0.05). Compared with the circ_0000212 interference group, the numbers of clone formed and migrating and invading HCC9204 cells in the interference circ_0000212+miR-139-5p inhibitor group were significantly increased (P < 0.05), and the inhibition rate and apoptosis rate were significantly reduced (P < 0.05). Compared with the paclitaxel group, the numbers of clones formed and migrating and invading HCC9204 cells in the paclitaxel + circ_0000212 interference group were significantly reduced (P < 0.05), and the inhibition rate and apoptosis rate were significantly increased (P < 0.05). Compared with the paclitaxel + circ_0000212 interference group, the numbers of clones formed and migrating and invading HCC9204 cells in the paclitaxel + circ_0000212 interference + miR-139-5p inhibitor group were significantly increased (P < 0.05), and the inhibition rate and apoptosis rate were significantly reduced (P < 0.05).
CONCLUSION Interfering with circ_0000212 can inhibit cell proliferation, migration, and invasion, induce cell apoptosis, and increase its sensitivity to paclitaxel in liver cancer cells by targeting and up-regulating miR-139-5p.
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Affiliation(s)
- Hui-Zhong Zhang
- Department of Hepatobiliary and Pancreatogastric Surgery, Jinhua Guangfu Cancer Hospital, Jinhua 321111, Zhejiang Province, China
| | - Xiao-Dong Zhang
- Department of Hepatobiliary and Pancreatogastric Surgery, Jinhua Guangfu Cancer Hospital, Jinhua 321111, Zhejiang Province, China
| | - Jian-Xin Huang
- Department of Hepatobiliary and Pancreatogastric Surgery, Jinhua Guangfu Cancer Hospital, Jinhua 321111, Zhejiang Province, China
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Shan L, Hou X. Circular RNA hsa_circ_0026552 inhibits the proliferation, migration and invasion of trophoblast cells via the miR‑331‑3p/TGF‑βR1 axis in pre‑eclampsia. Mol Med Rep 2021; 24:798. [PMID: 34523694 PMCID: PMC8456345 DOI: 10.3892/mmr.2021.12438] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 05/24/2021] [Indexed: 12/01/2022] Open
Abstract
Globally, pre-eclampsia (PE) is a gestational disorder that causes increased morbidity of the fetus and mortality induced by pregnancy. Despite various studies, the understanding of the causes or mechanism of the development of PE remains elusive. Thus, the present study aimed to investigate the role of circular (circ)RNA hsa_circ_0026552 (hsa_circ_0026552) in the development of PE and its mechanism of regulation. hsa_circ_0026552 differential expression in PE tissue data and clinical samples were analyzed and it was observed that hsa_circ_0026552 is highly upregulated in PE samples. Furthermore, miR-331-3p was detected as an hsa_circ_0026552 target miRNA and TGF-βR1 gene as a target of miR-331-3p. These results were confirmed using various assays, including dual-luciferase reporter, reverse transcription-quantitative PCR and RNA pull-down assay. It was observed that miR-331-3p expression was negatively correlated to hsa_circ_0026552 relative expression, while TGF-βR1 expression was positively correlated to hsa_circ_0026552 expression evaluated by Pearson's correlation test. The functional experiments, including Cell Counting Kit-8, colony formation and Transwell assay, showed that silencing hsa_circ_0026552 could significantly strengthen the proliferation, migration and invasion of the trophoblastic HTR-8/SVneo cells, but the subsequent overexpression of hsa_circ_0026552 reversed this. Mechanistically, it was concluded that hsa_circ_0026552 acts as a miR-331-3p sponge to upregulate TGF-βR1 expression in trophoblasts and is involved significantly in PE development and progression in pregnant women. The circRNA hsa_circ_0026552 could be a novel therapeutic target and prognostic biomarker for PE.
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Affiliation(s)
- Li Shan
- Department of Obstetrics, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
| | - Xiaofei Hou
- Department of Prenatal Screening Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
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Bing ZX, Zhang JQ, Wang GG, Wang YQ, Wang TG, Li DQ. Silencing of circ_0000517 suppresses proliferation, glycolysis, and glutamine decomposition of non-small cell lung cancer by modulating miR-330-5p/YY1 signal pathway. Kaohsiung J Med Sci 2021; 37:1027-1037. [PMID: 34405943 DOI: 10.1002/kjm2.12440] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 06/23/2021] [Accepted: 07/19/2021] [Indexed: 12/14/2022] Open
Abstract
In recent years, circular RNA (circRNA) has been found to be involved in a variety of cancer processes. More and more attention has been paid to the research of circRNA in lung cancer. This study aims to investigate whether circ_0000517 affected the physiology of non-small cell lung cancer (NSCLC) and the underlying mechanism. The results demonstrated that circ_0000517 was highly expressed in lung cancer tissues and cells, and overexpression of circ_0000517 was negatively correlated with the prognosis of NSCLC patients. Silencing of circ_0000517 significantly inhibited the proliferation, glycolysis, and glutamine decomposition of NSCLC cells in vitro and repressed the growth of xenografted tumors in vivo. Moreover, knockdown of circ_0000517 attenuated the expression of PCNA, HK2, LDHA, ASCT2, and GLS1. Further study found that circ_0000517 targeted miR-330-5p and miR-330-5p targeted YY1. In addition, miR-330-5p inhibitor reversed inhibition of cancer cell proliferation, glycolysis, and glutamine decomposition induced by si-circ_0000517. In conclusion, our study revealed that silencing of circ_0000517 improved the progression of NSCLC through regulating miR-330-5p/YY1 axis.
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Affiliation(s)
- Zhong-Xing Bing
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Jia-Qi Zhang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Gui-Ge Wang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Yan-Qing Wang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Tian-Ge Wang
- Chinese Academy of Medical Sciences Plastic Surgery Hospital, Beijing, China
| | - Dan-Qing Li
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China
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He H, Li J, Luo M, Wei Q. Inhibitory role of circRNA_100395 in the proliferation and metastasis of prostate cancer cells. J Int Med Res 2021; 49:300060521992215. [PMID: 33641485 PMCID: PMC7917968 DOI: 10.1177/0300060521992215] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE Circular RNAs (circRNAs) are non-coding RNAs with high cancer-specific expression and the potential for regulating tumorigenesis. CircRNA_100395 is expressed at low levels in many cancers and is involved in the regulation of tumor cell proliferation and metastasis. However, its expression and function in prostate cancer remain unclear. METHODS Endogenous expression levels of circRNA_100395 and microRNA-1228 (miR-1228) in prostate cancer tissue samples and cell lines were detected by quantitative reverse transcription-polymerase chain reaction. Cell proliferation, invasion, and migration, cell cycle distribution, and epithelial-mesenchymal transition (EMT) were analyzed in circRNA_100395-overexpressing prostate cancer cells by Cell Counting Kit-8, flow cytometry, Transwell assay, and western blotting, respectively. RESULTS CircRNA_100395 expression was downregulated in cancerous prostate tissues relative to adjacent normal tissues. CircRNA_100395 expression was negatively correlated with tumor size, Gleason score, tumor stage, and lymph node metastasis. Moreover, circRNA_100395 overexpression inhibited cell proliferation, altered cell cycle distribution, reduced cell migration and invasion abilities, and suppressed EMT in prostate cancer cells. Moreover, miR-1228 was a direct downstream target of circRNA_100395, and the anti-tumor ability of circRNA_100395 was significantly reversed by miR-1228. CONCLUSION This study identified circRNA_100395 as an anti-tumor circRNA and a potential therapeutic target for prostate cancer.
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Affiliation(s)
- Haitian He
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.,Department of Urology, Shenzhen Nanshan District Shekou People's Hospital, Shenzhen, Guangdong, China
| | - Jianhua Li
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Mayao Luo
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qiang Wei
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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14
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Cheng Z, Liu G, Huang C, Zhao X. Upregulation of circRNA_100395 sponges miR-142-3p to inhibit gastric cancer progression by targeting the PI3K/AKT axis. Oncol Lett 2021; 21:419. [PMID: 33841580 PMCID: PMC8020390 DOI: 10.3892/ol.2021.12680] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 01/20/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) has a high morbidity and mortality, hence it is very important to elucidate the molecular pathogenesis mechanism of GC progression in order to find new treatment strategies. The present study aimed to explore the biological function of circular RNA_100395 (circRNA_100395) in GC. The expression level of circRNA_100395 in GC tissues, as well as normal epithelial cells and various gastric cancer cell lines, was detected using reverse transcription-quantitative PCR. Cell Counting Kit-8, EdU assay, flow cytometry and Transwell assays were performed to investigate cell proliferation, apoptosis, migration and invasion, respectively. A dual-luciferase reporter assay was performed to detect the correlation between circRNA_100395 and micro (mi)RNA-142-3p. Western blotting was performed to elucidate the potential regulatory mechanism. circRNA_100395 expression was found to be increased in GC tissues and cell lines. However, miR-142-3p expression was significantly reduced. Besides, low expression levels of circRNA_100395 were associated with poor tumor differentiation, advanced Tumor-Node-Metastasis stage, lymph node metastasis and shorter overall survival time. Moreover, overexpression of circRNA_100395 suppressed cell proliferation, increased the apoptosis rate and suppressed cell invasion and migration by inhibiting the PI3K/AKT signaling pathway. These findings also showed that miRNA-142-3p rescued the antitumor effects induced by circRNA_100395-overexpression. cirRNA_100395-overexpression had antitumor effects via regulating the miR-142-3p signaling pathway, which might be a promising treatment target for GC.
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Affiliation(s)
- Zhiyi Cheng
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Guiyuan Liu
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Chuanjiang Huang
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Xiaojun Zhao
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
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15
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Zhang C, Cao J, Lv W, Mou H. CircRNA_100395 Carried by Exosomes From Adipose-Derived Mesenchymal Stem Cells Inhibits the Malignant Transformation of Non-Small Cell Lung Carcinoma Through the miR-141-3p-LATS2 Axis. Front Cell Dev Biol 2021; 9:663147. [PMID: 33842488 PMCID: PMC8027360 DOI: 10.3389/fcell.2021.663147] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/05/2021] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE The specific purpose of this study is to investigate the impact exosomes from adipose-derived mesenchymal stem cell (AMSC) has on non-small cell lung carcinoma (NSCLC) and the relative applications. METHODS circ_100395, miR-141-3p, and LATS2 were expressed and detected in NSCLC and paracancerous tissues as well as NSCLC cell lines. Pearson correlation analysis, Dual-Luciferase Reporter Assay and RNA pull-down assay were used to validate their expression and interaction, respectively. After isolation and culture of AMSCs, exosomes were extracted and identified. EdU, epithelial-mesenchymal transition (EMT), and cell colony formation assay were used to distinguish the biological activity of the cells. Expression Hippo/YAP signalling pathway-related proteins were measured by western blotting. Subsequently, tumour volume and weight were confirmed based on xenograft nude mice models, Ki-67 and LATS2 expression was observed by immunohistochemistry. RESULTS circ_100395 was lowly expressed in NSCLC tissues or cells. The negative correlations and interactions were confirmed between circ_100395 and miR-141-3p, miR-141-3p, and LATS2. AMSC-derived exosomes with overexpression of circ_100395 (exo-circ_100395) significantly inhibited the biological activity as well as EMT of H1650 cells and Hippo/YAP signalling pathway activity. In addition, exo-circ_100395 markedly reduced tumour volume and weight as well as Ki-67 and LASP1 expression in vivo. However, overexpressed miR-141-3p or knocked down LATS2 alleviated the above effects. CONCLUSION Exo-circ_100395 can increase LATS2 expression by sponging miR-141-3p to regulate Hippo/YAP signalling pathway, thereby inhibiting NSCLC malignant transformation.
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Affiliation(s)
- Chong Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jinlin Cao
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wang Lv
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Haibo Mou
- Department of Medical Oncology, Shulan (Hangzhou) Hospital, Affiliated to Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
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Xiong G, Zhang J, Zhang Y, Pang X, Wang B, Zhang Y. Circular RNA_0074027 participates in cell proliferation, apoptosis and metastasis of colorectal cancer cells through regulation of miR‑525‑3p. Mol Med Rep 2021; 23:324. [PMID: 33760126 PMCID: PMC7974509 DOI: 10.3892/mmr.2021.11963] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 01/21/2021] [Indexed: 12/25/2022] Open
Abstract
The present study aimed to elucidate the biological function of circular RNAs (circRNA) 0074027 in colorectal cancer (CRC). The expression of circRNA‑0074027 in CRC tissues and cells was determined by reverse transcription‑quantitative PCR. The in vitro experiments, including Cell Counting Kit‑8 (CCK‑8) assay, 5‑Ethynyl‑2'‑deoxyuridine assay, flow cytometry and Transwell assay, were applied to evaluate cell proliferation, apoptosis and metastasis ability respectively following downregulation of circRNA‑0074027. The correlation between circRNA‑0074027 and micro (mi)RNA‑525‑3p was determined via dual‑luciferase reporter assay. Finally, western blotting was used to explore the possible regulatory mechanism. CircRNA‑0074027 was upregulated in CRC tissues, while miR‑525‑3p expression was reduced. In addition, patients with CRC and circRNA‑0074027 overexpression were more likely to have low tumor differentiation, lymph node metastasis and advanced TMN stage. Deletion of circRNA‑0074027 could suppress cell proliferation and metastasis through up-regulating p53 expression and forbidding epithelial‑mesenchymal transition signaling pathway. The addition of miRNA‑525‑3p inhibitors could reverse the anti‑tumor effects induced by the deletion of circRNA‑0074027. The downregulation of cirRNA_0074027 inhibited tumor progression via sponging miR‑525‑3p, which could be a promising treatment bio‑marker for CRC.
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Affiliation(s)
- Gang Xiong
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Jun Zhang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Yichao Zhang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Xiao Pang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Biao Wang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Yongchuan Zhang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
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Tao X, Shao Y, Yan J, Yang L, Ye Q, Wang Q, Lu R, Guo J. Biological roles and potential clinical values of circular RNAs in gastrointestinal malignancies. Cancer Biol Med 2021; 18:j.issn.2095-3941.2020.0348. [PMID: 33710802 PMCID: PMC8185857 DOI: 10.20892/j.issn.2095-3941.2020.0348] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 11/19/2020] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs), a class of endogenous RNA molecules, are produced by alternative splicing of precursor RNA and are covalently linked at the 5' and 3' ends. Recent studies have revealed that dysregulated circRNAs are closely related to the occurrence and progression of gastrointestinal malignancies. Accumulating evidence indicates that circRNAs, including circPVT1, circLARP4, circ-SFMBT2, cir-ITCH, circRNA_100782, circ_100395, circ-DONSON, hsa_circ_0001368, circNRIP1, circFAT1(e2), circCCDC66, circSMARCA5, circ-ZNF652, and circ_0030235 play important roles in the proliferation, differentiation, invasion, and metastasis of cancer cells through a variety of mechanisms, such as acting as microRNA sponges, interacting with RNA-binding proteins, regulating gene transcription and alternative splicing, and being translated into proteins. With the characteristics of high abundance, high stability, extensive functions, and certain tissue-, time- and disease-specific expressions, circRNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.
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Affiliation(s)
- Xueping Tao
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Yongfu Shao
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Jianing Yan
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Liyang Yang
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Qihua Ye
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Qingling Wang
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Rongdan Lu
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
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18
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Guan B, Li Q, Zhang HZ, Yang HS. circ_NOTCH3 Functions as a Protooncogene Competing With miR-205-5p, Modulating KLF12 Expression and Promoting the Development and Progression of Basal-Like Breast Carcinoma. Front Oncol 2021; 10:602694. [PMID: 33552974 PMCID: PMC7857013 DOI: 10.3389/fonc.2020.602694] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 11/30/2020] [Indexed: 12/12/2022] Open
Abstract
Breast cancer is the most common type of cancer diagnosed among women, and basal-like breast carcinoma (BLBC) has been associated with a more aggressive histology, poorer prognosis, and non-responsiveness to hormone therapy. In the present study, the role and molecular mechanism of circular (circ)_NOTCH3 in the development and progression for BLBC was identified. circ_RNAs array was used to screen the ectopic expression of hsa_circ_0109177 (circ_NOTCH3) in BLBC. RT-qPCR was conducted to evaluate the circ_NOTCH3 expression in BLBC tissues and paired normal tissues, as well as related cell lines. Cell function changes were analyzed following circ_NOTCH3 or micro (mi)RNA overexpression or co-expression. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the binding sites between circ_NOTCH3 and miRNAs. Gene expression changes were assessed using western blotting. circ_NOTCH3 had a significantly higher expression in BLBC tissues and cell lines. The upregulation of circ_NOTCH3 promoted the proliferation, migration, invasion and inhibited the apoptosis for BLBC cells. The opposite results were observed following miR-205-5p overexpression. However, the co-expression of circ_NOTCH3 and miR-205-5p resulted in those restoration. circ_NOTCH3 is capable of binding to miR-205-5p, and upregulating its target gene KLF12, which can be downregulated by miR-205-5p overexpression and restored by the co-expression of circ_NOTCH3 and miR205-5p. circ_NOTCH3, being an protooncogene and a powerful biomarker, can function as a sponge, compete with miR-205-5p, modulate KLF12 expression, and promote the development and progression of BLBC.
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Affiliation(s)
- Bing Guan
- Department of Pathology, Shanghai 6th People's Hospital Jinshan Branch, Shanghai, China
| | - Qing Li
- Department of Pathology, Shanghai Pudong New Area People's Hospital, Shanghai, China
| | - Hui-Zhen Zhang
- Department of Pathology, Shanghai 6th People's Hospital, Shanghai, China
| | - Hai-Sheng Yang
- Department of Pathology, Shanghai 6th People's Hospital Jinshan Branch, Shanghai, China
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Comprehensive Analysis of Differentially Expressed circRNAs Reveals a Colorectal Cancer-Related ceRNA Network. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2020; 2020:7159340. [PMID: 32952599 PMCID: PMC7481959 DOI: 10.1155/2020/7159340] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 07/25/2020] [Indexed: 12/15/2022]
Abstract
The morbidity and mortality of colorectal cancer (CRC) remained to be very high worldwide. Recently, circRNAs had been revealed to have a crucial role in cancer prognosis and progression. Numerous researches have shown that RNA sequencing technology and in silico method were widely used to identify pathogenic mechanisms and uncover promising targets for diagnosis and therapy. In this study, these methods were analyzed to obtain differentially expressed circRNAs (DECs). We identified upregulated 316 circRNAs and reduced 76 circRNAs in CRC samples, in comparison with those in normal tissues. In addition, a competitive endogenous network of circRNA-miRNA-mRNA was established to predict the mechanisms of circRNAs. Bioinformatics analysis revealed that these circRNAs participated in metabolism regulation and cell cycle progression. Of note, we observed the hub genes and miRNAs in this ceRNA network were associated with the survival time in CRC. We think this study could provide potential prognostic biomarkers and targets for CRC.
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20
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Wang HY, Wang YP, Zeng X, Zheng Y, Guo QH, Ji R, Zhou YN. Circular RNA is a popular molecule in tumors of the digestive system (Review). Int J Oncol 2020; 57:21-42. [PMID: 32377736 PMCID: PMC7252451 DOI: 10.3892/ijo.2020.5054] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/06/2020] [Indexed: 02/06/2023] Open
Abstract
Most tumors of the digestive system, including esophageal, gastric, liver and colorectal cancer, are malignant tumors that are associated with rates of high morbidity and mortality. The lack of effective methods for early diagnosis is an important cause of poor prognosis for these malignancies. Circular RNAs (circRNAs) belong to a family of endogenous, covalently closed non‑coding RNAs that are characterized as having no 5' cap structures or 3' poly‑A tails. Shortly following discovery, circRNAs were considered to be a product of mis‑splicing and have no significant biological function. However, in recent years, accumulating evidence is demonstrating that they serve key roles in tumorigenesis and have the potential to serve as diagnostic markers. The present article summarizes the biogenesis and function of circRNAs and reviews their role in seven common types of tumor of the digestive system whilst exploring their potential as tumor markers and the significant roles they can serve in the digestive system, in addition to providing a referencing point for future studies of digestive system malignancies.
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Affiliation(s)
- Hao-Ying Wang
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yu-Ping Wang
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Xi Zeng
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Ya Zheng
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Qing-Hong Guo
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Rui Ji
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yong-Ning Zhou
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
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21
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Gao AM, Yuan C, Hu AX, Liu XS. circ_ARF3 regulates the pathogenesis of osteosarcoma by sponging miR-1299 to maintain CDK6 expression. Cell Signal 2020; 72:109622. [PMID: 32240746 DOI: 10.1016/j.cellsig.2020.109622] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/21/2020] [Accepted: 03/28/2020] [Indexed: 12/19/2022]
Abstract
Increasing evidence suggests that circular RNAs are emerging biomarkers or targets for early cancer diagnosis and treatment. However, the studies of circular RNA in osteosarcoma (OS) are limited. In this study we found that circ_ARF3 were highly expressed in osteosarcoma cell lines and tumor tissues. Knocking down circ_ARF3 greatly ceased OS cell growth, impaired cell colony formation and halted cell cycle transition from G1 to S phase. Bioinformatic analysis suggested that miR-1299 is the target of circ_ARF3. Luciferase assay and biotin labeled circ_ARF3 pull down assay confirmed their interactions in OS cells. The regulatory roles of circ_ARF3 on miR-1299 was also investigated. Further bioinformatic analysis showed that CDK6 is the target of miR-1299. Overexpressing miR-1299 in OS cells decreased CDK6 expression and arrested OS cell growth and cell cycle progression. However, the roles of miR-1299 in regulating CDK6 expression, OS cell growth and cell cycle progression were greatly impaired in the presence of circ_ARF3. In general, our study demonstrated that in the OS, highly expressed circ_ARF3 acts as a sponge of miR-1299 to inhibit miR-1299 mediated CDK6 downregulation which further promoted OS pathogenesis. circ_ARF3 could be a potential target for OS treatment in the future.
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Affiliation(s)
- Ai-Mei Gao
- Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Chunyan Yuan
- Department of Pathology, Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Ai-Xin Hu
- Department of Orthopaedics, The People's Hospital of China Three Gorges University, Yichang, Hubei, China
| | - Xiang-Sheng Liu
- Department of Orthopaedics, The Fifth People's Hospital of Fudan University, Heqing Road No.801, Minghang District, Shanghai 200240, China.
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22
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Wang F, Xu X, Zhang N, Chen Z. Identification and integrated analysis of hepatocellular carcinoma-related circular RNA signature. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:294. [PMID: 32355738 PMCID: PMC7186732 DOI: 10.21037/atm.2020.03.06] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Circular RNAs (circRNAs), a novel type of non-coding RNA, play a vital role in the pathogenesis and development of cancer. CircRNAs signatures may be useful as prognostic and predictive factors as well as clinical tools for evaluating disease status and prognosis. This study was carried out to explore novel circRNA signatures in hepatocellular carcinoma (HCC). Methods The expression profiles of circRNAs were retrieved from the Gene Expression Omnibus (GEO). The expression profiles of miRNAs and mRNAs were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The results of the microarray were validated by quantitative real-time RCR (qPCR). Based on circRNA-miRNA pairs and miRNA-mRNA pairs, a competitive endogenous RNA (ceRNA) network was constructed. Functional analysis was performed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA). Furthermore, survival analysis was carried out using the Kaplan-Meier curve and the log-rank test. Results Differentially expressed circRNAs in HCC from GEO databases (GSE94508 and GSE97332) were screened and analyzed using the bioinformatics method. We detected a total of 26 differentially expressed circRNAs by qPCR and then selected 6 circRNAs to construct the circRNA-miRNA-mRNA networks. Through prognostic analysis, 3 target hub genes (AURKA, KIF5B, and RHOA) of circRNAs were discovered. Moreover, GSEA and GSVA were used to reveal the functions of AURKA, KIF5B, and RHOA in HCC. Conclusions We identified three hub genes, and our results suggest that the circHMGCS1/miR-581/AURKA, circHMGCS1/miR-892a/KIF5B, and circTMCO3/miR-577/RHOA axes may play a vital role in HCC progression.
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Affiliation(s)
- Feiran Wang
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226000, China
| | - Xiaodong Xu
- Department of General Surgery, the 4th Affiliated Hospital of Nantong University, Yancheng 224000, China
| | - Nannan Zhang
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226000, China
| | - Zhong Chen
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226000, China
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Liu J, Li Z, Teng W, Ye X. Identification of downregulated circRNAs from tissue and plasma of patients with gastric cancer and construction of a circRNA-miRNA-mRNA network. J Cell Biochem 2020; 121:4590-4600. [PMID: 32052496 DOI: 10.1002/jcb.29673] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 01/24/2020] [Indexed: 12/26/2022]
Abstract
The connection between circular RNAs (circRNAs) and gastric cancer has been reported widely in recent years. However, previous studies have focused mainly on circRNAs from gastric cancer tissue. The objectives of the present study were to detect dysregulated circRNAs from both tissue and plasma of patients with gastric cancer and to explore their potential roles in the pathogenesis of gastric cancer. Expression profiles of circRNAs were obtained from the Gene Expression Omnibus (GEO) and analyzed using the GEO2R tool to identify differential expressed circRNAs. The significance threshold was set as |log2 (fold change)| > 2 and adjusted P < .05. The microRNA (miRNA) binding sites of the differentially expressed circRNAs were predicted using the Circular RNA Interactome web tool. TargetScan and the miRNet database were used to predict the miRNA target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using Database for Annotation Visualization and Integrated Discovery. Hub genes were identified and a network was constructed with Cytoscape. The overall survival rates for the selected miRNAs and messenger RNAs were evaluated by Kaplan-Meier Plotter. A total of three downregulated circRNAs (hsa_circ_0001190, hsa_circ_0036287, and hsa_circ_0048607) were identified in this study. Six miRNAs and eight hub genes met the significance criteria and were selected for further analysis. A circRNA-miRNA-hub gene network was constructed based on three circRNAs, six miRNAs, and eight hub genes. Evaluation of overall survival rates for the hub genes showed that low expression levels of GADD45A, PPP1CB, PJA2, and KLF2 were associated with poor overall survival. This study identified potential novel plasma circRNA biomarkers and provides insights into the underlying mechanisms of gastric cancer pathogenesis.
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Affiliation(s)
- Jingfu Liu
- Department of Blood Transfusion, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Zhen Li
- Department of Blood Transfusion, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Wenhao Teng
- Department of Gastrointestinal Surgery, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Xianren Ye
- Department of Blood Transfusion, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China.,Fujian Provincial Key Laboratory of Tumor Biotherapy, Fuzhou, Fujian, China
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