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Hirohata R, Yamamoto Y, Mimae T, Hamai Y, Ibuki Y, Takahashi RU, Okada M, Tahara H. Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy. Ann Surg Oncol 2025; 32:570-580. [PMID: 39419890 DOI: 10.1245/s10434-024-16247-z] [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: 07/05/2024] [Accepted: 09/10/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND The authors hypothesized that small ribonucleic acid (sRNA) obtained from blood samples after neoadjuvant therapy from patients treated with neoadjuvant chemoradiation therapy (NACRT) could serve as a novel biomarker for predicting pathologic complete response (pCR). METHODS This study included 99 patients treated with esophagectomy after NACRT between March 2010 and October 2021 whose blood samples were collected between the end of NACRT and surgery. Next-generation sequencing (NGS) was used to analyze sRNAs from the blood samples. A predictive model for pCR comprising micro-RNA isoforms (isomiR), transfer RNA (tRNA)-derived sRNAs (tsRNAs), and clinical factors was constructed using cross-validation. RESULTS Of the 99 patients, pCR was diagnosed for 30 and non-pCR for 69 of the patients. Among sRNAs, the isomiRs of let-7b and miR-93 and the tsRNA group derived from tRNA-Gly-CCC/GCC were identified as predictive factors. The clinical factors included a decrease in the maximum standardized uptake value (SUVmax) at the primary site, clinical complete response post-NACRT, preoperative biopsy, and post-NACRT carcinoembryonic antigen levels. The combined predictive model for pCR (C-PM) was established using the three sRNAs and four clinical factors. The area under the curve for the C-PM was 0.84, which was a significant factor in the multivariate analysis (odds ratio, 89.41; 95 % confidence interval 8.1-987.5; p < 0.001). CONCLUSIONS Pathologic complete response after NACRT can be predicted by a predictive model constructed from preoperative clinical factors obtained via minimally invasive procedures and sRNA identified by NGS. Preoperative pCR prediction may influence treatment decision-making after NACRT.
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Affiliation(s)
- Ryosuke Hirohata
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Yuki Yamamoto
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Takahiro Mimae
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Yoichi Hamai
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Yuta Ibuki
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Ryou-U Takahashi
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Hidetoshi Tahara
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
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Delek FSP, Tunçer ŞB, Ödemiş DA, Erciyas SK, Erdoğan ÖŞ, Saip P, Yazıcı H. miR-3653-3p Expression in PBMCs: Unveiling the Diagnostic Potential for Ovarian Cancer. Biochem Genet 2024:10.1007/s10528-024-10819-0. [PMID: 38705961 DOI: 10.1007/s10528-024-10819-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 04/18/2024] [Indexed: 05/07/2024]
Abstract
Ovarian cancer is typically diagnosed at an advanced stage, recurs early and often, and currently lacks effective treatment. Therefore, overall survival and progression-free survival are relatively short for this disease. Sensitive and specific biomarkers for early diagnosis and follow-up for effective treatment of the disease are currently lacking. MicroRNA (miRNA/miR) expression studies are widely used in cancer research. Disruption or malfunction of miRNAs, a class of noncoding small RNAs, has been implicated in cancer progression in several publications. Of note, the expression of a series of miRNAs is known to differ in ovarian cancer. In cancer research, it is crucial to analyze expression patterns in both cancer patients and healthy individuals to identify cancer-specific biological markers and to understand their role in cancer. In the present study, the expression levels of miR-3653-3p in the peripheral blood mononuclear cells (PBMCs) of 150 patients with high-risk ovarian cancer were determined, including those with a family history of cancer or an early-age diagnosis of ovarian cancer, as well as 100 healthy individuals. The results were then compared between the two groups. The expression level of miR-3653-3p in the PBMCs of patients with ovarian cancer was determined to be 9.49-fold higher than that in the healthy control group, and this result was statistically significant (P < 0.001). In addition, receiver-operating characteristic curve analysis of PBMC showed statistical significance of miR-3653-3p in discriminating ovarian cancer patients from healthy subjects (P < 0.001). These results suggest that miR-3653-3p detected in peripheral blood may be used as a non-invasive biomarker for ovarian cancer.
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Affiliation(s)
- Fatma Seher Pektopal Delek
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye
- Division of Cancer Genetics, Department of Basic Oncology, Institute of Health Sciences, Istanbul University, Vezneciler-Fatih, 32416, Istanbul, Türkiye
| | - Şeref Buğra Tunçer
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye
| | - Demet Akdeniz Ödemiş
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye
| | - Seda Kılıç Erciyas
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye
| | - Özge Şükrüoğlu Erdoğan
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye
| | - Pınar Saip
- Department of Clinical Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye
| | - Hülya Yazıcı
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Çapa-Fatih, 34093, Istanbul, Türkiye.
- Department of Medical Biology and Genetics, Faculty of Medicine, Istanbul Arel University, Cevizlibağ-Zeytinburnu, 34010, Istanbul, Türkiye.
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Yang Z, Guan F, Bronk L, Zhao L. Multi-omics approaches for biomarker discovery in predicting the response of esophageal cancer to neoadjuvant therapy: A multidimensional perspective. Pharmacol Ther 2024; 254:108591. [PMID: 38286161 DOI: 10.1016/j.pharmthera.2024.108591] [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: 08/23/2023] [Revised: 12/02/2023] [Accepted: 01/04/2024] [Indexed: 01/31/2024]
Abstract
Neoadjuvant chemoradiotherapy (NCRT) followed by surgery has been established as the standard treatment strategy for operable locally advanced esophageal cancer (EC). However, achieving pathologic complete response (pCR) or near pCR to NCRT is significantly associated with a considerable improvement in survival outcomes, while pCR patients may help organ preservation for patients by active surveillance to avoid planned surgery. Thus, there is an urgent need for improved biomarkers to predict EC chemoradiation response in research and clinical settings. Advances in multiple high-throughput technologies such as next-generation sequencing have facilitated the discovery of novel predictive biomarkers, specifically based on multi-omics data, including genomic/transcriptomic sequencings and proteomic/metabolomic mass spectra. The application of multi-omics data has shown the benefits in improving the understanding of underlying mechanisms of NCRT sensitivity/resistance in EC. Particularly, the prominent development of artificial intelligence (AI) has introduced a new direction in cancer research. The integration of multi-omics data has significantly advanced our knowledge of the disease and enabled the identification of valuable biomarkers for predicting treatment response from diverse dimension levels, especially with rapid advances in biotechnological and AI methodologies. Herein, we summarize the current status of research on the use of multi-omics technologies in predicting NCRT response for EC patients. Current limitations, challenges, and future perspectives of these multi-omics platforms will be addressed to assist in experimental designs and clinical use for further integrated analysis.
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Affiliation(s)
- Zhi Yang
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, China
| | - Fada Guan
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, United States of America
| | - Lawrence Bronk
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, China.
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Guan X, Pavani KC, Chunduru J, Broeckx BJG, Van Soom A, Peelman L. Hsa-miR-665 Is a Promising Biomarker in Cancer Prognosis. Cancers (Basel) 2023; 15:4915. [PMID: 37894282 PMCID: PMC10605552 DOI: 10.3390/cancers15204915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/29/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023] Open
Abstract
Biomarkers are biomolecules used to identify or predict the presence of a specific disease or condition. They play an important role in early diagnosis and may be crucial for treatment. MicroRNAs (miRNAs), a group of small non-coding RNAs, are more and more regarded as promising biomarkers for several reasons. Dysregulation of miRNAs has been linked with development of several diseases, including many different types of cancer, and abnormal levels can be present in early stages of tumor development. Because miRNAs are stable molecules secreted and freely circulating in blood and urine, they can be sampled with little or no invasion. Here, we present an overview of the current literature, focusing on the types of cancers for which dysregulation of miR-665 has been associated with disease progression, recurrence, and/or prognosis. It needs to be emphasized that the role of miR-665 sometimes seems ambiguous, in the sense that it can be upregulated in one cancer type and downregulated in another and can even change during the progression of the same cancer. Caution is thus needed before using miR-665 as a biomarker, and extrapolation between different cancer types is not advisable. Moreover, more detailed understanding of the different roles of miR-665 will help in determining its potential as a diagnostic and prognostic biomarker.
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Affiliation(s)
- Xuefeng Guan
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium; (X.G.); (B.J.G.B.)
| | - Krishna Chaitanya Pavani
- Department of Internal Medicine, Reproduction and Population Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; (K.C.P.); (A.V.S.)
- Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Gent, Belgium
| | - Jayendra Chunduru
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA;
| | - Bart J. G. Broeckx
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium; (X.G.); (B.J.G.B.)
| | - Ann Van Soom
- Department of Internal Medicine, Reproduction and Population Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; (K.C.P.); (A.V.S.)
| | - Luc Peelman
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium; (X.G.); (B.J.G.B.)
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Huang J, Yang Y, Zhao F, Zhang Z, Deng J, Lu W, Jiang X. LncRNA SATB2-AS1 overexpression represses the development of hepatocellular carcinoma through regulating the miR-3678-3p/GRIM-19 axis. Cancer Cell Int 2023; 23:82. [PMID: 37118800 PMCID: PMC10148439 DOI: 10.1186/s12935-023-02901-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 03/24/2023] [Indexed: 04/30/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignancy worldwide with one of the worst prognoses. Emerging studies have revealed that long noncoding RNAs (lncRNAs) contribute to HCC progression. This research probes the expression and regulatory effect of lncRNA SATB2-AS1 on HCC development. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to measure the SATB2-AS1 profile in HCC tissues and adjacent non-tumor tissues. The impact of SATB2-AS1, miR-3678-3p, or GRIM-19 on HCC cell proliferation, growth, migration, invasion, and apoptosis was determined by gain- and loss-of-function experiments. The results revealed that SATB2-AS1 was downregulated in HCC tissues, and its lower levels were related to higher tumor staging and poorer prognosis of HCC patients. SATB2-AS1 overexpression repressed HCC cell proliferation, induced G1 arrest, and apoptosis, and inhibited migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, SATB2-AS1 inactivated STAT3/HIF-1α and strengthened GRIM-19 expression. After knocking down GRIM-19 with small interfering RNA (siRNA), the malignant phenotypes of HCC cells were enhanced. Further bioinformatics analysis showed that miR-3678-3p was targeted by SATB2-AS1. The dual-luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Fluorescence in situ Hybridization (FISH) test confirmed that SATB2-AS1 sponged miR-3678-3p and the latter targeted GRIM-19. The rescue experiments showed that miR-3678-3p aggravated the malignant behaviors of HCC cells, whereas SATB2-AS1 overexpression reversed miR-3678-3p-mediated effects. Inhibition STAT3 promoted SATB2-AS1 and GRIM-19 expression, and reduced miR-3678-3p level. Activation STAT3 exerted opposite effects. Overall, this study confirmed that SATB2-AS1 is a potential prognostic biomarker for HCC and regulates HCC devolvement by regulating the miR-3678-3p/GRIM-19/STAT3/HIF-1α pathway.
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Affiliation(s)
- Jiang Huang
- Department of Pharmacy, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Yunfang Yang
- Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Fulan Zhao
- Department of Pharmacy, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Zhuo Zhang
- Department of Pharmacology, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Jian Deng
- Department of Pharmacy, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Wei Lu
- Department of Emergency, Luzhou People's Hospital, Luzhou, 646000, Sichuan, China
| | - Xian Jiang
- Department of Anesthesiology, Luzhou People's Hospital, No. 316, Jiugu Avenue 2, Jiangyang District, Luzhou, 646000, Sichuan, China.
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Yang Y, Zhang H, Liu Z, Ma N, Li C, Wang Y, Li Z. Use of exosome transcriptome-based analysis to identify novel biomarkers in patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy. ANNALS OF TRANSLATIONAL MEDICINE 2023; 11:182. [PMID: 36923096 PMCID: PMC10009568 DOI: 10.21037/atm-23-452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 02/15/2023] [Indexed: 03/06/2023]
Abstract
Background The prognosis of esophageal squamous cell carcinoma (ESCC) is improved by neoadjuvant chemoradiotherapy (nCRT), especially for patients with pathologic complete response (pCR). Despite the efforts to predict treatment response using multimodality, no molecule has proven to be a strong biomarker. This study aimed to profile the expression of exosome transcriptome that could predict pCR in ESCC before and after nCRT. Methods We collected paired blood samples of 15 patients with ESCC who received nCRT and radical surgery. They were divided into 3 groups: (A) residual tumor in the first clinical response evaluation (CRE-1), (B) no residual tumor in CRE-1 but with residual tumor in CRE-2 which was performed after 5-6 weeks, and (C) no residual tumor in CRE-1 or CRE-2. For each patient, the blood sample was collected before nCRT (time point 0); and then 6 weeks after nCRT, the clinical response was evaluated, and another blood sample was collected (time point 1). Results Using the intersection of different sets, we found 23 progression-associated messenger RNAs (mRNAs) and 67 remission-associated mRNAs. Between remission-associated mRNAs and the targets of progression-associated (carcinogenic) microRNAs (miRNAs), the intersection was acquired, and 2 miRNA-mRNA networks (IFIT2-miR-3615-IFIT2-miR-484 and BTN3A3-miR-6803-3p) were identified. Among the intersection of progression-associated (carcinogenic) mRNAs and the targets of remission-associated miRNAs, there is a network with miR-132-3p (remission-associated miRNA) located at the core, matched with DICER1, KLHL8, ANKRD12, ASH1L, and IMP4. Conclusions Our findings identified altered plasma exosome RNAs among the different groups and between different time points of nCRT, as well as the corresponding enrichments and regulatory networks, which may serve as potentially predictors of treatment response for patients with ESCC after nCRT.
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Affiliation(s)
- Yang Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Zhang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhichao Liu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ning Ma
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chunguang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Wang
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Noncoding RNAs in esophageal cancer: A glimpse into implications for therapy resistance. Pharmacol Res 2023; 188:106678. [PMID: 36709789 DOI: 10.1016/j.phrs.2023.106678] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 01/09/2023] [Accepted: 01/25/2023] [Indexed: 01/27/2023]
Abstract
Esophageal cancer (EC) is one of the most common malignancies of the digestive system and has a high morbidity and mortality worldwide. Chemotherapy in combination with radiotherapy is one of the most important treatment modalities for EC. Chemoradiotherapy is currently acknowledged worldwide as being the standard treatment for locally advanced or unresectable disease. Unfortunately, due to the existence of therapy resistance, a number of EC patients fail to benefit from drug or irradiation treatment, which ultimately leads to poor outcomes. Considerable efforts have been made to explore the mechanisms underlying the therapy resistance of EC. Notably, noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are current research areas for the modulation of therapy responses and may serve as new targets to overcome treatment resistance in EC. Herein, we summarized the mechanisms by which ncRNAs are involved in drug and radiation resistance in EC and highlighted their role in promoting or repressing treatment resistance. Additionally, we discussed the clinical relevance of ncRNAs, which may serve as potential therapeutic targets and predictive biomarkers for EC.
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Zhang X, Lu M, Zhu J, Zhang C, Wang M. Altered genome‑wide hydroxymethylation analysis for neoadjuvant chemoradiotherapy followed by surgery in esophageal cancer. Exp Ther Med 2022; 25:29. [PMID: 36561617 PMCID: PMC9748644 DOI: 10.3892/etm.2022.11728] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 10/14/2022] [Indexed: 11/26/2022] Open
Abstract
Esophageal cancer has high incidence rate in China. Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for esophageal squamous cell carcinoma (ESCC). However, there are few reliable epigenetic parameters for patients with ESCC undergoing neoadjuvant therapy. Genomic extract from tumor tissue was amplified and sequenced using the Illumina HiSeq4000 to quantify genes associated methylation or hydromethylation in 12 patients with ESCC undergoing nCRT. The genome-wide hydroxymethylation were analyzed by methylated and hydroxymethylated DNA immunoprecipitation sequencing by MACS2 software and UCSC RefSeq database. Abnormal DNA methylation was statistically different between nCRT-well (showed a pathological complete response to nCRT) and nCRT-poor (showed incomplete pathological response to nCRT) patients. Levels of ten-eleven translocation 1, 2 and 3 mRNA and protein were higher in tumor tissue in nCRT-well group patients than in nCRT-poor group patients. Illumina HiSeq 4000 sequencing identified 2925 hypo-differentially hydroxymethylated region (DhMRs) and 292 hyper-DhMRs in promoter between nCRT-well and nCRT-poor patients. Biological processes associated with hyper-DhMRs included 'snRNA processing', 'hormone-mediated signaling pathway' and 'cellular response'. Metabolic processes were associated with hypo-DhMRs. These data may explain the functional response to nCRT in patients with abnormal promoter of methylation gene-associated mRNA expression. The present results implied that hyper-DhMRs and hypo-DhMRs affect molecular pathways, such as hippo and Notch signaling pathways, highlighting epigenetic modifications associated with clinical response to nCRT in patients with esophageal cancer.
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Affiliation(s)
- Xianjing Zhang
- The Second Clinical Department, Medical School of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Mingzhu Lu
- Department of Pathology, Changzhou Cancer Hospital, Soochow University, Changzhou, Jiangsu 213032, P.R. China
| | - Jing Zhu
- Department of Laboratory Medicine, Suzhou Science and Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China
| | - Changsong Zhang
- Department of Laboratory Medicine, Suzhou Science and Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China,Correspondence to: Dr Changsong Zhang, Department of Laboratory Medicine, Suzhou Science and Technology Town Hospital, Gusu School, Nanjing Medical University, 1 Lijiang Road, Suzhou, Jiangsu 215153, P.R. China
| | - Meihua Wang
- Department of Pathology, Changzhou Cancer Hospital, Soochow University, Changzhou, Jiangsu 213032, P.R. China,Correspondence to: Dr Changsong Zhang, Department of Laboratory Medicine, Suzhou Science and Technology Town Hospital, Gusu School, Nanjing Medical University, 1 Lijiang Road, Suzhou, Jiangsu 215153, P.R. China
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A Transcriptomic Liquid Biopsy Assay for Predicting Resistance to Neoadjuvant Therapy in Esophageal Squamous Cell Carcinoma. Ann Surg 2022; 276:101-110. [PMID: 35703443 PMCID: PMC9276630 DOI: 10.1097/sla.0000000000005473] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to establish a liquid-biopsy assay to predict response to neoadjuvant therapy (NAT) in esophageal squamous cell carcinoma (ESCC) patients. SUMMARY BACKGROUND DATA Pretreatment prediction of resistance to NAT is of great significance for the selection of treatment options in ESCC patients. In this study, we comprehensively translated tissue-based microRNA (miRNA) and messenger RNA (mRNA) expression biomarkers into a liquid biopsy assay. METHODS We analyzed 186 clinical ESCC samples, which included 128 formalin-fixed paraffin-embedded and a matched subset of 58 serum samples, from 2 independent institutions. We performed quantitative reverse-transcription polymerase chain reaction, and developed a resistance-prediction model using the logistic regression analyses. RESULTS We first evaluated the potential of 4-miRNAs and 3-mRNAs panel, which robustly predicted resistance to NAT [area under the curve (AUC): 0.85]. Moreover, addition of tumor size to this panel increased predictive potential to establish a combination signature (AUC: 0.92). We successfully validated this signature performance in independent cohort, and our model was more accurate when the signature was combined with clinical predictors (AUC: 0.81) to establish a NAT resistance risk (NATRR) model. Finally, we successfully translated our NATRR model into a liquid biopsy assay (AUC: 0.78), and a multivariate regression analysis revealed this model as an independent predictor for response to NAT (odds ratio: 6.10; P < 0.01). CONCLUSIONS We successfully developed a liquid biopsy-based assay that allows robust prediction of response to NAT in ESCC patients, and our assay provides fundamentals of developing precision-medicine.
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Zhang Q, Wang Z, Zhang Z, Zhu L, Yang X. Analysis of microarray-identified genes and MicroRNAs associated with Trifluridine resistance in colorectal cancer. ALL LIFE 2022. [DOI: 10.1080/26895293.2022.2080280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Qiqi Zhang
- Department of Integrated Chinese and Western Medicine, Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China
| | - Zhan Wang
- Department of Medical Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China
| | - Zhenghua Zhang
- Department of Clinical Oncology, Jing’An District Centre Hospital of Shanghai, Huashan Hospital Fudan University Jing’An Branch, Shanghai, People’s Republic of China
| | - Lifei Zhu
- Cancer Center, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, People’s Republic of China
| | - Xijing Yang
- Department of Biotherapy, The Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai, People’s Republic of China
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Matou-Nasri S, Najdi M, AlSaud NA, Alhaidan Y, Al-Eidi H, Alatar G, AlWadaani D, Trivilegio T, AlSubait A, AlTuwaijri A, Abudawood M, Almuzzaini B. Blockade of p38 MAPK overcomes AML stem cell line KG1a resistance to 5-Fluorouridine and the impact on miRNA profiling. PLoS One 2022; 17:e0267855. [PMID: 35511922 PMCID: PMC9071118 DOI: 10.1371/journal.pone.0267855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/16/2022] [Indexed: 11/19/2022] Open
Abstract
Most of the AML patients in remission develop multidrug resistance after the first-line therapy and relapse. AML stem cells have gained attention for their chemoresistance potentials. Chemoresistance is a multifactorial process resulting from altered survival signaling pathways and apoptosis regulators such as MAPK, NF-κB activation and ROS production. We targeted the survival pathway p38 MAPK, NF-κB and ROS generation in human chemoresistant AML stem cell line KG1a, susceptible to enhance cell sensitivity to the chemotherapy drug 5-Fluorouridine, compared to the chemosensitive AML cell line HL60. After confirming the phenotypic characterization of KG1a and HL60 cells using flow cytometry and transcriptomic array analyses, cell treatment with the NF-κB inhibitor IKKVII resulted in a complete induction of apoptosis, and a few p38 MAPK inhibitor SB202190-treated cells underwent apoptosis. No change in the apoptosis status was observed in the ROS scavenger N-acetylcysteine-treated cells. The p38 MAPK pathway blockade enhanced the KG1a cell sensitivity to 5-Fluorouridine, which was associated with the upregulation of microribonucleic acid-(miR-)328-3p, as determined by the microarray-based miRNA transcriptomic analysis. The downregulation of the miR-210-5p in SB202190-treated KG1a cells exposed to FUrd was monitored using RT-qPCR. The miR-328-3p is known for the enhancement of cancer cell chemosensitivity and apoptosis induction, and the downregulation of miR-210-5p is found in AML patients in complete remission. In conclusion, we highlighted the key role of the p38 MAPK survival pathway in the chemoresistance capacity of the AML stem cells and potentially involved miRNAs, which may pave the way for the development of a new therapeutic strategy targeting survival signaling proteins and reduce the rate of AML relapse.
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Affiliation(s)
- Sabine Matou-Nasri
- Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- * E-mail: (SMN); (BA)
| | - Maria Najdi
- Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- Postgraduate program, King Saud University, Riyadh, Saudi Arabia
| | - Nouran Abu AlSaud
- Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Yazeid Alhaidan
- Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Hamad Al-Eidi
- Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Ghada Alatar
- Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Deemah AlWadaani
- Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Thadeo Trivilegio
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Arwa AlSubait
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Abeer AlTuwaijri
- Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
| | - Manal Abudawood
- Department of Clinical Laboratory Sciences, Chair of Medical and Molecular Genetics Research, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Bader Almuzzaini
- Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- * E-mail: (SMN); (BA)
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12
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Li M, Cai O, Yu Y, Tan S. Paeonol inhibits the malignancy of Apatinib-resistant gastric cancer cells via LINC00665/miR-665/MAPK1 axis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 96:153903. [PMID: 35026514 DOI: 10.1016/j.phymed.2021.153903] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 12/16/2021] [Accepted: 12/19/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Paeonol is the extractive of Paeonia suffruticosa Andr and is reported to reverse the chemotherapy resistance of cancer cells. The present study explores the role of paeonol in inhibiting the malignant biological behaviors of Apatinib-resistant gastric cancer (GC) cells. METHODS The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was adopted to screen the target genes of paeonol, and the STRING database was employed to construct a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the target genes was performed employing DAVID online database. The expressions of these target genes in GC tissues and para-cancerous tissues were analyzed with GEPIA database, and GEO datasets (GSE109476 and GSE93415) were utilized to analyze differentially expressed lncRNAs and miRNAs in GC tissues and para-cancerous tissues. The expressions of LINC00665, miR-665 and MAPK1 mRNA in Apatinib-resistant GC cells were detected through quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay was conducted to detect cell proliferation; Transwell assays were employed to detect cell migration and invasion, and TdT-mediated dUTP nick end labeling (TUNEL) assay was utilized to detect cell apoptosis. Dual-luciferase reporter gene assay was performed to detect the binding relationships between miR-665 and LINC00665, as well as between miR-665 and MAPK1 mRNA. The expressions of MAPK1 protein and glycolysis-associated proteins (GLUT1, LDHB and HK2) were detected by Western blot. Additionally, a tumor xenograft mice model was constructed to evaluate the effects of paeonol on lung metastasis. RESULTS Paeonol could inhibit the proliferation, migration, invasion and glycolysis, and promote the apoptosis of Apatinib-resistant GC cells. TCMSP database suggested that Paeonol had 17 target genes, and 17 target genes were mainly enriched in signaling pathways related to apoptosis, glucose and lipid metabolism, etc.; GEPIA database suggests that MAPK1, among the 17 target genes, was markedly elevated in GC tissues. Paeonol could decrease LINC00665 and MAPK1 expressions in GC cells but increase the expression of miR-665. LINC00665 overexpression, MAPK1 overexpression or inhibition of miR-665 could abolish the inhibitive effects of paeonol on the malignant phenotypes of Apatinib-resistant GC cells. miR-665 is verified as an upstream regulator of MAPK1 and a target of LINC00665. Additionally, paeonol could significantly inhibit the lung metastasis in the tumor xenograft mice model. CONCLUSIONS Paeonol can inhibit the malignancy of Apatinib-resistant GC cells through LINC00665/miR-665/MAPK1 axis. For the first time, our study imply that paeonol may be a potential drug to reverse Apatinib-resistant of GC cells.
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Affiliation(s)
- Ming Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China; Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China
| | - Ou Cai
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China; Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China
| | - Yuanjie Yu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China; Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China.
| | - Shiyun Tan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China; Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No.99, Wuchang District, Wuhan 430060, Hubei, China
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13
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Li Y, Liu J, Cai XW, Li HX, Cheng Y, Dong XH, Yu W, Fu XL. Biomarkers for the prediction of esophageal cancer neoadjuvant chemoradiotherapy response: A systemic review. Crit Rev Oncol Hematol 2021; 167:103466. [PMID: 34508841 DOI: 10.1016/j.critrevonc.2021.103466] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 08/04/2021] [Accepted: 08/29/2021] [Indexed: 11/18/2022] Open
Abstract
Neoadjuvant chemoradiotherapy followed by surgery has been established as the standard treatment for locally advanced esophageal cancer. For patients with complete regression after neoadjuvant chemotherapy, active surveillance rather than planned surgery has been proposed as an organ preservation strategy. Reliable biomarkers to predict chemoradiation response is needed. We first summarized the previous reports of biomarkers with the potential to predict the treatment response of esophageal cancer neoadjuvant chemoradiotherapy. These traditional biomarkers are classified into three groups: genetic biomarkers, RNA biomarkers, and protein biomarkers. We then summarized some special types of biomarkers, including metabolites biomarkers, immune and tumor microenvironment biomarkers, and microbiome biomarkers.
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Affiliation(s)
- Yue Li
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jun Liu
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xu-Wei Cai
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Hong-Xuan Li
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Cheng
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao-Huan Dong
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Wen Yu
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
| | - Xiao-Long Fu
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
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14
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Choi JH, Kwon SM, Moon SU, Yoon S, Shah M, Lee BG, Yang J, Park YN, Wang HJ, Woo HG. TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659. Liver Int 2021; 41:2788-2800. [PMID: 34328265 DOI: 10.1111/liv.15026] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 07/22/2021] [Accepted: 07/23/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND & AIMS Noncoding RNAs (ncRNAs) play critical roles in hepatocellular carcinoma (HCC) progression. Here, by performing RNA-sequencing (RNA-Seq) profiling, we sought to identify novel ncRNAs that potentially drive the heterogeneous progression of liver cancers. METHODS RNA-Seq profiles were obtained from 68 HCC specimens and 10 samples of adjacent non-tumour liver tissues. The functional significance of the potential driver ncRNAs was evaluated by cell experiments. RESULTS TPRG1-AS1 was identified as a potential driver noncoding RNA that promotes heterogeneous liver cancer progression. TPRG1-AS1 induced tumour suppressor RNA-binding motif protein 24 (RBM24), suppressing tumour growth by activating apoptotic tumour cell death. In addition, we report that TPRG1-AS1 acts as a competing endogenous RNA (ceRNA) for RBM24, sponging miR-4691-5p and miR-3659 to interfere with their binding to RBM24. CONCLUSIONS We suggest that TPRG1-AS1 is a novel ceRNA sponging miR-4691-5p and miR-3659, resulting in RBM24 expression and suppression of liver cancer growth. Our results provide new insights into the functions of ncRNAs in heterogeneous HCC progression.
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Affiliation(s)
- Ji-Hye Choi
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - So M Kwon
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Sung U Moon
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Sarah Yoon
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.,Department of Biomedical Science, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Masaud Shah
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Byoung G Lee
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.,Department of Biomedical Science, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Jieun Yang
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.,Department of Biomedical Science, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Young N Park
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.,BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hee-Jung Wang
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hyun G Woo
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.,Department of Biomedical Science, Graduate School, Ajou University, Suwon, Republic of Korea
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15
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The critical function of miR-1323/Il6 axis in children with Mycoplasma pneumoniae pneumonia. J Pediatr (Rio J) 2021; 97:552-558. [PMID: 33347836 PMCID: PMC9432136 DOI: 10.1016/j.jped.2020.11.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/02/2020] [Accepted: 11/05/2020] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory infection in children. Tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and IL-6 have correlation with Mycoplasma pneumoniae lung infection and MPP pathogenesis. METHOD miRNAs participate in the pathogenesis of various diseases by regulating the development and differentiation of the immune cell. Blood was collected and total RNA was isolated. miRNA microarrays were performed to identify differentially expressed miRNAs in MPP patients. The levels of relative miRNAs and mRNAs were evaluated by qRT-PCR. RESULTS There are 23 differentially expressed miRNAs in MPP children's plasma, 15 miRNAs had enhanced expression and 8 had depressed expression. MPP patients showed lower mir-1323 level in blood samples than healthy controls. MPP patients with pleural effusion had much higher Il6 and Il17a mRNA levels than those without pleural effusion. The expression level of Il6 had a negative correlation with miR-1323 level. In the human THP-1 cell line, the level of miR-1323 was significantly reduced through lipopolysaccharides treatment. In THP-1 cells, overexpression or silencing of miR-1323 significantly reduced or promoted Il6 expression. CONCLUSION In conclusion, miR-1323 targets the mRNA of Il6 and inhibits the expression of Il6. The pathogenesis of MPP inhibits the expression of miR-1323 in macrophages, triggers the overexpression of Il6, and enhances inflammation response.
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16
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Cui D, Cheung ALM. Roles of microRNAs in tumorigenesis and metastasis of esophageal squamous cell carcinoma. World J Clin Oncol 2021; 12:609-622. [PMID: 34513596 PMCID: PMC8394161 DOI: 10.5306/wjco.v12.i8.609] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/11/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer that is prevalent in Eastern Asia. Despite recent advances in therapy, the outcome of ESCC patients is still dismal. MicroRNAs (miRNAs) are non-coding RNAs which can negatively modulate gene expression at the post-transcriptional level. The involvement and roles of miRNAs have become one of the hot topics of cancer research in recent years. In ESCC, genetic variations within miRNA coding genes were found to have distinct epidemiological significance in different populations. Dysregulated expression of several miRNAs was reported to be associated with therapeutic response. Functionally, miRNAs can act either in an oncogenic or a tumor-suppressive manner during tumorigenesis of ESCC by interrupting signaling pathways associated with cell proliferation, metabolism, cancer stemness, and resistance to chemo- or radiotherapy. Moreover, miRNAs modulate metastasis of ESCC by targeting genes that regulate cytoskeleton dynamics, extracellular matrix remodeling, epithelial-mesenchymal transition, and tumor microenvironment. Most importantly, mounting evidence suggests that inhibiting oncogenic miRNAs or restoring the loss of tumor-suppressive miRNAs has therapeutic potential in the treatment of ESCC. Here, we review and discuss recent studies on the significance, biological functions, and therapeutic potential of miRNAs in tumorigenesis and metastasis of ESCC.
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Affiliation(s)
- Di Cui
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Annie LM Cheung
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong 999077, China
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17
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Song Q, Liu H, Li C, Liang H. miR-33a-5p inhibits the progression of esophageal cancer through the DKK1-mediated Wnt/β-catenin pathway. Aging (Albany NY) 2021; 13:20481-20494. [PMID: 34426559 PMCID: PMC8436944 DOI: 10.18632/aging.203430] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 06/19/2021] [Indexed: 01/04/2023]
Abstract
Esophageal cancer (EC) is one of the most lethal malignancies in humans, and multiple miRNAs have been identified to modulate EC progression by targeting different targets. However, the effect and related mechanism of microRNA-33a-5p (miR-33a-5p) on EC development remain elusive. In this study, we explored the clinical value, function, and possible mechanism of miR-33a-5p in EC. We uncovered that miR-33a-5p and DKK1 are involved in the progression of EC. Significantly, the expression levels of miR-33a-5p were reduced and DKK1 levels were elevated in serum and tissues of clinical EC samples and in EC cell lines. The downregulation of miR-33a-5p and DKK1 upregulation were related to high TNM staging and poor differentiation of patients. The area under the curves (AUCs) of miR-33a-5p and DKK1 for the occurrence of EC were 0.914 and 0.900, respectively. Down-regulation of miR-33a-5p or overexpression of DKK1 indicated a worse prognosis. The miR-33a-5p overexpression or DKK1 depletion induced apoptosis and repressed proliferation, migration, and invasion of EC cells. The repression of miR-33a-5p by inhibitor or DKK1 overexpression presented the conversed effects on EC cells. Mechanically, miR-33a-5p suppressed DKK1 expression, and miR-33a-5p targeted DKK1 to affect the biological behavior of EC through the Wnt/β-catenin pathway. Meanwhile, miR-33a-5p inhibited the tumor growth of EC in vivo. Thus, we concluded that miR-33a-5p inhibited the progression of EC through the DKK1-mediated Wnt/β-catenin pathway. MiR-33a-5p and DKK1 can be used as potential therapeutic targets of EC.
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Affiliation(s)
- Qingping Song
- Department of Surgery, Tumor Hospital of Liaocheng, Liaocheng 252000, Shandong, China
| | - Hui Liu
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264000, Shandong, China
| | - Chengyan Li
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264000, Shandong, China
| | - Haifeng Liang
- Department of Surgery, Tumor Hospital of Liaocheng, Liaocheng 252000, Shandong, China
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18
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Li H, Tong F, Meng R, Peng L, Wang J, Zhang R, Dong X. E2F1-mediated repression of WNT5A expression promotes brain metastasis dependent on the ERK1/2 pathway in EGFR-mutant non-small cell lung cancer. Cell Mol Life Sci 2021; 78:2877-2891. [PMID: 33078208 PMCID: PMC11072416 DOI: 10.1007/s00018-020-03678-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 09/30/2020] [Accepted: 10/06/2020] [Indexed: 12/11/2022]
Abstract
Brain metastasis (BM) is associated with poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutation reportedly enhances the development of BM. However, the exact mechanism of how EGFR-mutant NSCLC contributes to BM remains unknown. Herein, we found the protein WNT5A, was significantly downregulated in BM tissues and EGFR-mutant samples. In addition, the overexpression of WNT5A inhibited the growth, migration, and invasion of EGFR-mutant cells in vitro and retarded tumor growth and metastasis in vivo compared with the EGFR wide-type cells. We demonstrated a molecular mechanism whereby WNT5A be negatively regulated by transcription factor E2F1, and ERK1/2 inhibitor (U0126) suppressed E2F1's regulation of WNT5A expression in EGFR-mutant cells. Furthermore, WNT5A inhibited β-catenin activity and the transcriptional levels of its downstream genes in cancer progression. Our research revealed the role of WNT5A in NSCLC BM with EGFR mutation, and proved that E2F1-mediated repression of WNT5A was dependent on the ERK1/2 pathway, supporting the notion that targeting the ERK1/2-E2F1-WNT5A pathway could be an effective strategy for treating BM in EGFR-mutant NSCLC.
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Affiliation(s)
- Huanhuan Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China
| | - Fan Tong
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China
| | - Rui Meng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China
| | - Ling Peng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China
| | - Jiaojiao Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China
| | - Ruiguang Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China
| | - Xiaorong Dong
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China.
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19
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Lin D, Chen X, Tan L. The predictive value of microRNAs for pathological response after neoadjuvant treatment in esophageal squamous cell carcinoma: a systematic review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:420. [PMID: 33842641 PMCID: PMC8033340 DOI: 10.21037/atm-20-3000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Neoadjuvant treatment followed by esophagectomy has been the standard strategy for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Pathological response after neoadjuvant treatment is of vital importance in the determination of long-term survival. Due to the involvement of microRNAs (miRNAs) in ESCC, some studies have proposed miRNA models to predict the pathological response. We aimed to summarize current studies on the predictive value of the miRNA models. We searched the relevant studies on PubMed, Web of Science and Cochrane Library up to February 14, 2020, using the following search term: (esophageal OR esophagus OR oesophageal OR oesophagus) AND (miR OR miRNA OR microRNA) AND (neoadjuvant OR preoperative OR induction). The initial search retrieved 206 studies. We briefly summarized the involvement of miRNAs in the origin, development and chemo- and radioresistance in ESCC. Then, 9 studies were enrolled in the systematic review. A great heterogeneity was observed across these studies. Of the 6 studies with diagnostic tests, the area under curve varied a lot. Although much evidence demonstrated the correlation between miRNAs and pathological response after in ESCC, the current studies has not established any promising models. A well-designed prospective study is essential to investigate the potential predictive models for pathological response after neoadjuvant treatment in ESCC.
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Affiliation(s)
- Dong Lin
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Xiaosang Chen
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
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20
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Xu Y, Liu M. MicroRNA-1323 downregulation promotes migration and invasion of breast cancer cells by targeting tumour protein D52. J Biochem 2021; 168:83-91. [PMID: 32211853 DOI: 10.1093/jb/mvaa035] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 02/23/2020] [Indexed: 02/06/2023] Open
Abstract
Breast cancer (BC) is one of the most common malignancies globally in women, with high mortality rate as a result of tumour metastasis. MicroRNAs play vital roles in the occurrence and development of human cancer. This study aimed to investigate the biological roles of miR-1323 in BC. The expression levels of miR-1323 were detected by quantitative real-time PCR assay. The effect of miR-1323 on BC cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Wound healing analysis and Matrigel Transwell assay were conducted to evaluate miR-1323-mediated BC cell migration and invasion. A luciferase reporter assay was used to test the target of miR-1323. We found that miR-1323 levels were downregulated in BC tissues and serums. Low-miR-1323 levels were associated with lymph node metastasis and advanced clinical stage. Tumour protein D52 (TPD52) was identified as a direct target of miR-1323. Low expression of miR-1323 contributed to the overexpression of TPD52 leading to enhanced BC progression. Our findings suggest that silencing of miR-1323 enhances BC development by regulating TPD52 expression, suggesting that miR-1323 and TPD52 may serve as potential therapeutic targets for BC treatment.
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Affiliation(s)
- Yuanying Xu
- Department of Ultrasonography, Yantai Yuhuangding Hospital, No. 20 Yuhuangding Este Road, Zhifu District, Yantai 264000, Shandong, China
| | - Meiyan Liu
- Department of Ultrasound Medicine, Outpatient Department, Yantai Affiliated Hospital, Binzhou Medical College, No. 717 Jinbu Street, Yantai 264100, Shandong, China
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21
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Lavery A, Turkington RC. Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer. Gastroenterol Rep (Oxf) 2020; 8:411-424. [PMID: 33442473 PMCID: PMC7793050 DOI: 10.1093/gastro/goaa065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 04/21/2020] [Accepted: 07/15/2020] [Indexed: 02/07/2023] Open
Abstract
Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide. In the setting of resectable disease, there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival. Disappointingly, only 15%-30% of patients obtain a histopathological response to neoadjuvant therapy, often at the expense of significant toxicity. There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes. In this review, we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting. We place these issues in the wider context of recommendations for biomarker development and reporting. The majority of studies focus on messenger RNA (mRNA) and microRNA (miRNA) biomarkers. These studies report a range of different genes involved in a wide variety of pathways and biological processes, and this is explained to a large extent by the different platforms and analysis methods used. Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker. Multiple molecular subtypes of oesophageal cancer have been proposed, although little is known about how these relate to clinical outcomes. We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.
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Affiliation(s)
- Anita Lavery
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, UK
| | - Richard C Turkington
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, UK
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22
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Chen Z, Yao N, Gu H, Song Y, Ye Z, Li L, Lu P, Shao Q. Circular RNA_LARP4 Sponges miR-1323 and Hampers Progression of Esophageal Squamous Cell Carcinoma Through Modulating PTEN/PI3K/AKT Pathway. Dig Dis Sci 2020; 65:2272-2283. [PMID: 31897898 DOI: 10.1007/s10620-019-05973-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 11/22/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Emerged as important regulators in cancer progression, circular RNAs have been tested to participate in diverse biological processes. Former studies have suggested that circular RNA_LARP4 (circLARP4) exerts indispensable function on the development of different cancers such as gastric cancer and ovarian cancer. Nonetheless, the specific role of circLARP4 has not been discovered in ESCC. AIMS The aim of this study is to explore the biological function and regulatory mechanism of circLARP4 in ESCC. METHODS CircLARP4, miR-1323, and PTEN expression levels were quantified by RT-qPCR. CCK-8, EdU, caspase-3 activity, wound healing, transwell, and western blot assays were chosen to assess ESCC cell growth. Luciferase reporter, RIP, and RNA pull-down assays were performed to examine the interaction between miR-1323 and circLARP4 (or PTEN). RESULTS CircLARP4 expression was observably downregulated in ESCC cell lines, and overexpressed circLARP4 restrained cell proliferation and migration whereas boosted cell apoptosis in ESCC. Molecular mechanism experiments revealed that circLARP4 could act as a sponge for miR-1323 and negatively modulated miR-1323 expression in ESCC. Interestingly, the repression of miR-1323 was correlated with inhibitive cell proliferation, migration, and promotive apoptosis. Besides, miR-1323 bound with PTEN, and PTEN expression was negatively regulated by miR-1323 whereas positively regulated by circLARP4 in ESCC. Moreover, rescue assays testified that miR-1323 overexpression or PTEN deficiency could countervail the function of circLARP4 overexpression on ESCC progression. More importantly, circLARP4 played an inhibitory role in PI3K/AKT pathway. CONCLUSIONS CircLARP4 sponges miR-1323 and hampers tumorigenesis of ESCC through modulating PTEN/PI3K/AKT pathway.
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Affiliation(s)
- Zhiming Chen
- Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Ninghua Yao
- Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Hongmei Gu
- Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Yao Song
- Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Zhihui Ye
- Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Li Li
- Department of Chemotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Pengpeng Lu
- Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China
| | - Qi Shao
- Department of Chemotherapy, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China.
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Mahawongkajit P, Tomtitchong P. Expression of miRNA in 5-FU resistant esophageal cancer. Mol Clin Oncol 2020; 13:221-227. [PMID: 32714549 PMCID: PMC7366237 DOI: 10.3892/mco.2020.2070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 05/04/2020] [Indexed: 02/06/2023] Open
Abstract
Fluoropyrimidine plus platinum (FP) are chemotherapeutic drugs that are most frequently used to treat esophageal squamous cell carcinoma (ESCC). However, drug resistance often occurs, and the mechanisms of resistance to 5-FU is yet to be determined. The role of micro (mi)RNAs has been well established in a variety of human cancers. The aim of the present study was to investigate the expression profile of ESCC, revealing the differential expression between ESCC and 5-FU resistant ESCC. The establishment of a 5-FU resistant (5-FUR) cell lines model provides a way of analyzing the expression of miRNAs in drug resistance. The miRNA expression indicated 50 miRNAs that were upregulated in TE10-5-FUR compared with TE10, while 119 miRNAs were downregulated. The TE11-5-FUR demonstrated 140 miRNAs were upregulated compared with TE11, which exhibited 12 downregulated miRNAs. Both cell lines share the 2 candidate upregulated miRNAs (miR-146a and miR-483-5p) and 5 downregulated miRNAs (miR-34a, miR-141, miR-200b, miR-200c and miR-205). Further studies are required to analyze and evaluate the function of the miRNAs.
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Affiliation(s)
- Prasit Mahawongkajit
- Department of Surgery, Faculty of Medicine, Thammasat University, Amphur Klongluang, Pathumthani 12120, Thailand
| | - Prakitpunthu Tomtitchong
- Department of Surgery, Faculty of Medicine, Thammasat University, Amphur Klongluang, Pathumthani 12120, Thailand
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Identification of Differentially Expressed Genes and miRNAs Associated with Esophageal Squamous Cell Carcinoma by Integrated Analysis of Microarray Data. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1980921. [PMID: 32714975 PMCID: PMC7352135 DOI: 10.1155/2020/1980921] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 06/10/2020] [Indexed: 11/28/2022]
Abstract
To identify candidate key genes and miRNAs associated with esophageal squamous cell carcinoma (ESCC) development and prognosis, the gene expression profiles and miRNA microarray data including GSE20347, GSE38129, GSE23400, and GSE55856 were downloaded from the Gene Expression Omnibus (GEO) database. Clinical and survival data were retrieved from The Cancer Genome Atlas (TCGA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed genes (DEGs) was analyzed via DAVID, while the DEG-associated protein-protein interaction network (PPI) was constructed using the STRING database. Additionally, the miRNA target gene regulatory network and miRNA coregulatory network were constructed, using the Cytoscape software. Survival analysis and prognostic model construction were performed via the survival (version 2.42-6) and rbsurv R packages, respectively. The results showed a total of 2575, 2111, and 1205 DEGs, and 226 differentially expressed miRNAs (DEMs) were identified. Pathway enrichment analyses revealed that DEGs were mainly enriched in 36 pathways, such as the proteasome, p53, and beta-alanine metabolism pathways. Furthermore, 448 nodes and 1144 interactions were identified in the PPI network, with MYC having the highest random walk score. In addition, 7 DEMs in the microarray data, including miR-196a, miR-21, miR-205, miR-194, miR-103, miR-223, and miR-375, were found in the regulatory network. Moreover, several reported disease-related miRNAs, including miR-198a, miR-103, miR-223, miR-21, miR-194, and miR-375, were found to have common target genes with other DEMs. Survival analysis revealed that 85 DEMs were related to prognosis, among which hsa-miR-1248, hsa-miR-1291, hsa-miR-421, and hsa-miR-7-5p were used for a prognostic survival model. Taken together, this study revealed the important roles of DEGs and DEMs in ESCC development, as well as DEMs in the prognosis of ESCC. This will provide potential therapeutic targets and prognostic predictors for ESCC.
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Ritter A, Hirschfeld M, Berner K, Jaeger M, Grundner-Culemann F, Schlosser P, Asberger J, Weiss D, Noethling C, Mayer S, Erbes T. Discovery of potential serum and urine-based microRNA as minimally-invasive biomarkers for breast and gynecological cancer. Cancer Biomark 2020; 27:225-242. [PMID: 32083575 DOI: 10.3233/cbm-190575] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Deregulated microRNAs (miRNAs) in breast and gynecological cancer might contribute to improve early detection of female malignancies. OBJECTIVE Specification of miRNA types in serum and urine as minimally-invasive biomarkers for breast (BC), endometrial (EC) and ovarian cancer (OC). METHODS In a discovery phase, serum and urine samples from 17 BC, five EC and five OC patients vs. ten healthy controls (CTRL) were analyzed with Agilent human miRNA microarray chip. Selected miRNA types were further investigated by RT-qPCR in serum (31 BC, 13 EC, 15 OC patients, 32 CTRL) and urine (25 BC, 10 EC, 10 OC patients, 30 CTRL) applying two-sample t-tests. RESULTS Several miRNA biomarker candidates exhibited diagnostic features due to distinctive expression levels (serum: 26; urine: 22). Among these, miR-518b, -4719 and -6757-3p were found specifically deregulated in BC serum. Four, non-entity-specific, novel biomarker candidates with unknown functional roles were identified in urine (miR-3973; -4426; -5089-5p and -6841). RT-qPCR identified miR-484/-23a (all p⩽ 0.001) in serum as potential diagnostic markers for EC and OC while miR-23a may also serve as an endogenous control in BC diagnosis. CONCLUSIONS Promising miRNAs as liquid biopsy-based tools in the detection of BC, EC and OC qualified for external validation in larger cohorts.
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Affiliation(s)
- Andrea Ritter
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marc Hirschfeld
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany
| | - Kai Berner
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Markus Jaeger
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Franziska Grundner-Culemann
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Pascal Schlosser
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Jasmin Asberger
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Daniela Weiss
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Claudia Noethling
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Sebastian Mayer
- Department of Gynecology and Obstetrics, Hospital Memmingen, Memmingen, Germany
| | - Thalia Erbes
- Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Abramovic I, Ulamec M, Katusic Bojanac A, Bulic-Jakus F, Jezek D, Sincic N. miRNA in prostate cancer: challenges toward translation. Epigenomics 2020; 12:543-558. [PMID: 32267174 DOI: 10.2217/epi-2019-0275] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based literature search was conducted with the last update in May 2019. After identifying critical variations in designs and protocols that undermined clear-cut evidence acquisition, and reliable translation into clinical practice, we propose guidelines for most critical steps that should be considered in future research of miRNA as biomarkers, especially in PCa.
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Affiliation(s)
- Irena Abramovic
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Monika Ulamec
- Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Ljudevit Jurak Clinical Department of Pathology & Cytology, University Clinical Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Department of Pathology, University of Zagreb, School of Dental Medicine & School of Medicine, Zagreb 10000, Croatia
| | - Ana Katusic Bojanac
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Floriana Bulic-Jakus
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Davor Jezek
- Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Department of Histology & Embryology, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Nino Sincic
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
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Wang B, Wang L, Mao J, Wen H, Xu L, Ren Y, Du H, Yang H. Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics. Mol Med Rep 2020; 21:2051-2062. [PMID: 32186775 PMCID: PMC7115213 DOI: 10.3892/mmr.2020.11025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 11/26/2019] [Indexed: 11/05/2022] Open
Abstract
Mesenchymal stem cells (MSCs) affect diverse aspects of tumor progression, such as angiogenesis, tumor growth and metastasis. Bone marrow MSCs (BM‑MSCs) are fibroblast‑like cells with multipotent differentiation ability, that localize to areas of tissue damage, including wounds and solid tumors. The tumor suppressor gene, p53, is functionally involved in cell cycle control, apoptosis and genomic stability, and is mutated and inactivated in most human cancers. The present study aimed to investigate the role of p53 in the biology of BM‑MSCs. In the present study, p53 wild‑type (p53+/+), knockdown (p53+/‑) and knockout (p53‑/‑) mouse BM‑MSCs (mBM‑MSCs) were observed to be similar in appearance and in the expression of cell surface biomarkers, but expressed differential p53 protein levels. The p53+/‑ and p53‑/‑ mBM‑MSCs demonstrated an increased proliferation rate compared with mBM‑MSCs derived from p53+/+ mice. mBM‑MSCs from all three groups, representing distinct p53 statuses, were unable to form tumors over a 3‑month period in vivo. The adipogenic and osteogenic differentiation of mBM‑MSCs was increased in the absence of p53. The colony formation and migratory abilities of p53+/‑ and p53‑/‑ mBM‑MSCs were markedly enhanced, and the expression levels of stem cell‑associated proteins were significantly increased compared with p53+/+. The expression levels of microRNA (miR)‑3152 and miR‑337 were significantly increased in p53+/‑ and p53‑/‑ mBM‑MSCs, whereas the expression levels of miR‑221, miR‑155, miR‑1288 and miR‑4669 were significantly decreased. The expression levels of tumor necrosis factor‑α and interferon‑γ‑inducible protein‑10 were significantly upregulated in the supernatant of p53+/‑ and p53‑/‑ mBM‑MSCs. Ubiquitin protein ligase E3 component n‑recognin 2, RING‑finger protein 31 and matrix metalloproteinase 19 were highly expressed in p53+/‑ and p53‑/‑ mBM‑MSCs. The results of the present study indicated that p53 may serve an important role in the biology of mBM‑MSCs, and may provide novel insights into the role of cells with different p53 statuses in cancer progression.
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Affiliation(s)
- Bo Wang
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Lingxia Wang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Jiahui Mao
- Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Huiyan Wen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Longjiang Xu
- Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Yang Ren
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Hong Du
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Huan Yang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
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Li CY, Zhang WW, Xiang JL, Wang XH, Li J, Wang JL. Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics. Chin Med J (Engl) 2019; 132:2213-2222. [PMID: 31490264 PMCID: PMC6797152 DOI: 10.1097/cm9.0000000000000427] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA). METHODS Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients' tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients' clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients' tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study. RESULTS Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients' tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients' tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar. CONCLUSION This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.
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Affiliation(s)
- Cheng-Yun Li
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China
| | - Wen-Wen Zhang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China
| | - Ji-Lian Xiang
- Department of Gastroenterology, Third People's Hospital of Gansu Province, Lanzhou, Gansu 730000, China
| | - Xing-Hua Wang
- Department of Gastrointestinal Surgery, Gansu Wuwei Tumor Hospital, Wuwei, Gansu 733000, China
| | - Jin Li
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China
| | - Jun-Ling Wang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China
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Liu NW, Huang X, Liu S, Lu Y. EXT1, Regulated by MiR-665, Promotes Cell Apoptosis via ERK1/2 Signaling Pathway in Acute Lymphoblastic Leukemia. Med Sci Monit 2019; 25:6491-6503. [PMID: 31465316 PMCID: PMC6733154 DOI: 10.12659/msm.918295] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background EXT1 is an endoplasmic reticulum-resident glycosyl transferase whose intracellular expression alters the biosynthesis and distribution of heparan sulfate. EXT1 is regarded as a classic tumor suppressor. MiR-665 can act as either an oncogene or tumor-suppressing gene in different tumors. The aim of the current study was to determine the function and molecular mechanisms of EXT1 and miR-665 in acute lymphoblastic leukemia (ALL). Material/Methods EXT1 expression in ALL was evaluated by real-time polymerase chain reaction (RT-PCR) and western blotting. The effects of EXT1 in ALL were explored by Cell Counting Kit-8 (CCK-8)/EdU assays, western blotting, flow cytometry, and in vivo tumorigenesis assays. Label-free quantification was used to detect differentially expressed proteins in EXT1-overexpressing Reh cells. Results EXT1 expression is downregulated in ALL and negatively correlated with miR-665 expression. Moreover, low EXT1 and high miR-665 expression levels in adult ALL bone marrow tissues are correlated with poor patient survival. Our study showed that EXT1 modulates the proliferation and apoptosis of ALL cells in vitro and in vivo and that miR-665 promotes cell growth and inhibits apoptosis by suppressing EXT1. EXT1 promotes cell apoptosis via deactivating the ERK1/2 pathway. Conclusions In conclusion, this study is the first to confirm the association between low EXT1 levels and several clinical features of ALL. Low bone marrow EXT1 levels independently predict poor prognoses in adult ALL patients. Thus, our study suggests that EXT1- or miR-665-targeted strategies can confer the therapeutic effect of promoting apoptosis by deactivating the ERK1/2 pathway.
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Affiliation(s)
- Na-Wei Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland).,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland)
| | - Xin Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland).,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland)
| | - Shuang Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland).,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland)
| | - Yue Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland).,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China (mainland)
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30
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Bibby BAS, Miranda CS, Reynolds JV, Cawthorne CJ, Maher SG. Silencing microRNA-330-5p increases MMP1 expression and promotes an invasive phenotype in oesophageal adenocarcinoma. BMC Cancer 2019; 19:784. [PMID: 31391080 PMCID: PMC6686260 DOI: 10.1186/s12885-019-5996-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 07/30/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Many patients diagnosed with oesophageal adenocarcinoma (OAC) present with advanced disease and approximately half present with metastatic disease. Patients with localised disease, who are managed with curative intent, frequently undergo neoadjuvant chemoradiotherapy. Unfortunately, ~ 70% of patients have little or no response to chemoradiotherapy. We previously identified miR-330-5p as being the most significantly downregulated microRNA in the pre-treatment OAC tumours of non-responders to treatment, but that loss of miR-330-5p had a limited impact on sensitivity to chemotherapy and radiation in vitro. Here, we further examined the impact of miR-330-5p loss on OAC biology. METHODS miR-330-5p was suppressed in OE33 OAC cells following stable transfection of a vector-driven anti-sense RNA. Whole transcriptome digital RNA-Seq was employed to identify miR-330-5p regulated genes, and qPCR was used for validation. Protein expression was assessed by protein array, Western blotting and zymography. Invasive potential was measured using a transwell assay system. Tumour xenograft growth profile studies were performed in immunocompromised CD1 mice. RESULTS In OE33 cells, suppression of miR-330-5p significantly altered expression of 42 genes, and several secreted proteases. MMP1 gene expression and protein secretion was significantly enhanced with miR-330-5p suppression. This corresponded to enhanced collagen invasion in vitro. In vivo, OE33-derived tumour xenografts with miR-330-5p suppression grew faster than controls. CONCLUSIONS Loss of miR-330-5p expression in OAC tumours may influence tumour cell invasive capacity, tumour growth and therapeutic sensitivity via alterations to the tumour microenvironment.
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Affiliation(s)
- Becky A S Bibby
- Cancer Biology and Therapeutics Lab, School of Life Sciences, University of Hull, Hull, HU6 7RX, UK.,Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester, M20 4GJ, UK
| | - Cecelia S Miranda
- PET Imaging Centre, School of Life Sciences, University of Hull, Hull, HU6 7RX, UK
| | - John V Reynolds
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland
| | | | - Stephen G Maher
- Cancer Biology and Therapeutics Lab, School of Life Sciences, University of Hull, Hull, HU6 7RX, UK. .,Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
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Klinge CM, Piell KM, Tooley CS, Rouchka EC. HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Sci Rep 2019; 9:9430. [PMID: 31263129 PMCID: PMC6603045 DOI: 10.1038/s41598-019-45636-8] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs are dysregulated in breast cancer. Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2/B1) is a reader of the N(6)-methyladenosine (m6A) mark in primary-miRNAs (pri-miRNAs) and promotes DROSHA processing to precursor-miRNAs (pre-miRNAs). We examined the expression of writers, readers, and erasers of m6A and report that HNRNPA2/B1 expression is higher in tamoxifen-resistant LCC9 breast cancer cells as compared to parental, tamoxifen-sensitive MCF-7 cells. To examine how increased expression of HNRNPA2/B1 affects miRNA expression, HNRNPA2/B1 was transiently overexpressed (~5.4-fold) in MCF-7 cells for whole genome miRNA profiling (miRNA-seq). 148 and 88 miRNAs were up- and down-regulated, respectively, 48 h after transfection and 177 and 172 up- and down-regulated, respectively, 72 h after transfection. MetaCore Enrichment analysis identified progesterone receptor action and transforming growth factor β (TGFβ) signaling via miRNA in breast cancer as pathways downstream of the upregulated miRNAs and TGFβ signaling via SMADs and Notch signaling as pathways of the downregulated miRNAs. GO biological processes for mRNA targets of HNRNPA2/B1-regulated miRNAs included response to estradiol and cell-substrate adhesion. qPCR confirmed HNRNPA2B1 downregulation of miR-29a-3p, miR-29b-3p, and miR-222 and upregulation of miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced MCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
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Affiliation(s)
- Carolyn M Klinge
- Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40292, USA.
| | - Kellianne M Piell
- Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40292, USA
| | - Christine Schaner Tooley
- Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, 14203, USA
| | - Eric C Rouchka
- Bioinformatics and Biomedical Computing Laboratory, Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY, 40292, USA
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Zhao XG, Hu JY, Tang J, Yi W, Zhang MY, Deng R, Mai SJ, Weng NQ, Wang RQ, Liu J, Zhang HZ, He JH, Wang HY. miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer. Cell Death Dis 2019; 10:479. [PMID: 31209222 PMCID: PMC6579763 DOI: 10.1038/s41419-019-1705-z] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 05/23/2019] [Indexed: 12/21/2022]
Abstract
Cancer metastasis is the main cause of death in breast cancer (BC) patients. Therefore, prediction and treatment of metastasis is critical for enhancing the survival of BC patients. In this study, we aimed to identify biomarkers that can predict metastasis of BC and elucidate the underlying mechanism of the functional involvement of such markers in metastasis. miRNA expression profile was analyzed using a custom microarray system in 422 BC tissues. The relationship between the upregulated miR-665, metastasis and survival of BC was analyzed and verified in another set of 161 BC samples. The biological function of miR-665 in BC carcinogenesis was explored with in vitro and in vivo methods. The target gene of miR-665 and its signaling cascade were also analyzed. There are 399 differentially expressed miRNAs between BC and noncancerous tissues, of which miR-665 is the most upregulated miRNA in the BC tissues compared with non-tumor breast tissues (P < 0.001). The expression of miR-665 predicts metastasis and poor survival in 422 BC patients, which is verified in another 161 BC patients and 2323 BC cases from online databases. Ectopic miR-665 expression promotes epithelial–mesenchymal transition (EMT), proliferation, migration and invasion of BC cells, and increases tumor growth and metastasis of BC in mice. Bioinformatics, luciferase assay and other methods showed that nuclear receptor subfamily 4 group A member 3 (NR4A3) is a target of miR-665 in BC. Mechanistically, we demonstrated that miR-665 promotes EMT, invasion and metastasis of BC via inhibiting NR4A3 to activate MAPK/ERK kinase (MEK) signaling pathway. Our study demonstrates that miR-665 upregulation is associated with metastasis and poor survival in BC patients, and mechanistically, miR-665 enhances progression of BC via NR4A3/MEK signaling pathway. This study provides a new potential prognostic biomarker and therapeutic target for BC patients.
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Affiliation(s)
- Xin-Ge Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Jing-Ye Hu
- Department of Basic Medicine, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002, China
| | - Jun Tang
- Department of Breast Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Wei Yi
- Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510060, China
| | - Mei-Yin Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Rong Deng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Shi-Juan Mai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Nuo-Qing Weng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Rui-Qi Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ji Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Hui-Zhong Zhang
- Department of Breast Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Jie-Hua He
- Department of Breast Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Hui-Yun Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
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Zhang F, Yang C, Xing Z, Liu P, Zhang B, Ma X, Huang L, Zhuang L. LncRNA GAS5-mediated miR-1323 promotes tumor progression by targeting TP53INP1 in hepatocellular carcinoma. Onco Targets Ther 2019; 12:4013-4023. [PMID: 31190897 PMCID: PMC6535457 DOI: 10.2147/ott.s209439] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 04/29/2019] [Indexed: 12/19/2022] Open
Abstract
Background: MiR-1323 was identified in 2006. Until now, the roles and mechanisms of miR-1323 in the progression of cancers including hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to investigate the expressions, roles and mechanisms of miR-1323 in HCC development. Methods: QRT-PCR was used to evaluate the expressions of miR-1323, GAS5 and TP53INP1 in HCC tissues and cell lines. CCK-8 assay, transwell invasion assay and flow cytometry assay were conducted to evaluate the proliferation, invasion and apoptosis of HCC cells. Luciferase assay was used to identify microRNA-target interaction. Results: Firstly, our results showed that miR-1323 promoted proliferation and invasion, and inhibited apoptosis of HCC cells. Secondly, we found that TP53INP1 was a direct target of miR-1323 and could reverse the effects of miR-1323 on proliferation, invasion and apoptosis of HCC cells. Thirdly, our results showed that long non-coding RNA (lncRNA) GAS5 and miR-1323 could interact with each other and affect biological processes of HCC cells. Furthermore, we identified the negative correlations between miR-1323 and TP53INP1, and between miR-1323 and GAS5 in tumor tissues of patients with HCC. Conclusion: Taken together, our study revealed the important roles of GAS5/miR-1323/TP53INP1 axis in HCC progression. This study also provided promising strategies for targeted therapy of patients with HCC.
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Affiliation(s)
- Fengjuan Zhang
- Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China
| | - Chao Yang
- Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China
| | - Zhiyuan Xing
- Department of General Surgery, The Second Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China
| | - Pei Liu
- Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China
| | - Bo Zhang
- Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, People's Republic of China
| | - Xiang Ma
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China
| | - Liuye Huang
- Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, People's Republic of China
| | - Likun Zhuang
- Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China
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Slotta-Huspenina J, Drecoll E, Feith M, Habermehl D, Combs SE, Weichert W, Bettstetter M, Becker K, Langer R. Correction to: MicroRNA expression profiling for the prediction of resistance to neoadjuvant radiochemotherapy in squamous cell carcinoma of the esophagus. J Transl Med 2018; 16:128. [PMID: 29769068 PMCID: PMC5954453 DOI: 10.1186/s12967-018-1513-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 05/08/2018] [Indexed: 11/10/2022] Open
Abstract
Following publication of the original article [1], the authors reported that for one of the authors, Stephanie E. Combs, the middle name was accidentally omitted. They also reported that for two of the authors, Daniel Habermehl and Stephanie E. Combs, two affiliations were accidentally omitted. In this Correction the incorrect and correct author name are shown and the two omitted affiliations are listed.
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Affiliation(s)
- Julia Slotta-Huspenina
- Institute of Pathology, Technische Universität München, Trogerstrasse 18, 81675, Munich, Germany
| | - Enken Drecoll
- Institute of Pathology, Technische Universität München, Trogerstrasse 18, 81675, Munich, Germany
| | - Marcus Feith
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675, Munich, Germany
| | - Daniel Habermehl
- Department of Radiation Oncology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675, Munich, Germany.,Department of Radiation Sciences (DRS), Institute of Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.,Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany
| | - Stephanie E Combs
- Department of Radiation Oncology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675, Munich, Germany.,Department of Radiation Sciences (DRS), Institute of Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.,Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany
| | - Wilko Weichert
- Institute of Pathology, Technische Universität München, Trogerstrasse 18, 81675, Munich, Germany
| | - Marcus Bettstetter
- Teilgemeinschaftspraxis Molekularpathologie Südbayern, Giesinger Bahnhofplatz 2, 81539, Munich, Germany
| | - Karen Becker
- Institute of Pathology, Technische Universität München, Trogerstrasse 18, 81675, Munich, Germany
| | - Rupert Langer
- Institute of Pathology, University of Bern, Murtenstrasse 31, 3008, Bern, Switzerland.
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