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1
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Skryabin GO, Beliaeva AA, Enikeev AD, Tchevkina EM. Extracellular Vesicle miRNAs in Diagnostics of Gastric Cancer. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:1211-1238. [PMID: 39218020 DOI: 10.1134/s0006297924070058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/24/2024] [Accepted: 05/30/2024] [Indexed: 09/04/2024]
Abstract
Gastric cancer (GC) poses a significant global health challenge because of its high mortality rate attributed to the late-stage diagnosis and lack of early symptoms. Early cancer diagnostics is crucial for improving the survival rates in GC patients, which emphasizes the importance of identifying GC markers for liquid biopsy. The review discusses a potential use of extracellular vesicle microRNAs (EV miRNAs) as biomarkers for the diagnostics and prognostics of GC. Methods. Original articles on the identification of EV miRNA as GC markers published in the Web of Science and Scopus indexed issues were selected from the PubMed and Google Scholar databases. We focused on the methodological aspects of EV analysis, including the choice of body fluid, methods for EV isolation and validation, and approaches for EV miRNA analysis. Conclusions. Out of 33 found articles, the majority of authors investigated blood-derived extracellular vesicles (EVs); only a few utilized EVs from other body fluids, including tissue-specific local biofluids (washing the tumor growth areas), which may be a promising source of EVs in the context of cancer diagnostics. GC-associated miRNAs identified in different studies using different methods of EV isolation and analysis varied considerably. However, three miRNAs (miR-10b, miR-21, and miR-92a) have been found in several independent studies and shown to be associated with GC in experimental models. Further studies are needed to determine the optimal miRNA marker panel. Another essential step necessary to improve the reliability and reproducibility of EV-based diagnostics is standardization of methodologies for EV handling and analysis of EV miRNA.
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Affiliation(s)
- Gleb O Skryabin
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia.
| | - Anastasiya A Beliaeva
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia
| | - Adel D Enikeev
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia
| | - Elena M Tchevkina
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia
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2
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Fathi D, Elballal MS, Elesawy AE, Abulsoud AI, Elshafei A, Elsakka EG, Ismail A, El-Mahdy HA, Elrebehy MA, Doghish AS. An emphasis on the interaction of signaling pathways highlights the role of miRNAs in the etiology and treatment resistance of gastric cancer. Life Sci 2023; 322:121667. [PMID: 37023952 DOI: 10.1016/j.lfs.2023.121667] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/01/2023] [Accepted: 04/03/2023] [Indexed: 04/07/2023]
Abstract
Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/β-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC treatment modalities.
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3
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Bi W, Li J, Xiong M, Pan B, Zhang Z, Nasifu L, He B, Wang P. The diagnostic and prognostic role of miR-27a in cancer. Pathol Res Pract 2023; 247:154544. [PMID: 37235911 DOI: 10.1016/j.prp.2023.154544] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/11/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023]
Abstract
MicroRNA-27a (miR-27a) has been reported to be abnormally expressed in patients with cancer, and it could play potential roles as a diagnostic and prognostic biomarker of cancers. However, the diagnostic and prognostic role remains unclear. Hence, this meta-analysis, based on published data, was conducted to assess the utility of miR-27a as a diagnostic and prognostic marker in various cancers. To identify eligible studies, databases: Web of Science, PubMed, and CNKI were searched, with 868 literatures obtained, 16 of which were included in the Meta-analysis. The pooled results of studies conducted with serum/plasma showed that miR-27a was a valuable diagnostic biomarker in cancers (area under curve (AUC)= 0.91, sensitivity (SEN)= 0.84, specificity (SPE)= 0.85), with the diagnostic value slightly reduced in tumor tissue samples (AUC=0.83, SEN=0.78, SPE: 0.74). Additionally, the pooled results revealed that high expression of miR-27a predicted poor prognosis of cancer in serum/plasma (hazard ratio (HR) = 0.63, PHeterogeneity = 0.278, I2= 21.50%) but not in tumor tissue (HR = 0.98, PHeterogeneity =0.577, I2= 0.0). In brief, our results suggested that miR-27a in serum/plasma or tumor tissue could act as a diagnostic biomarker, and that miR-27a in serum/plasma could predict cancer patients' survival.
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Affiliation(s)
- Wen Bi
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
| | - Jingjing Li
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
| | - Mengqiu Xiong
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
| | - Bei Pan
- Medical College, Southeast University, Nanjing 210006, China.
| | - Zhongqiu Zhang
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China.
| | - Lubanga Nasifu
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China; Department of Biology, Muni University, Arua, Uganda.
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210006, China.
| | - Ping Wang
- School of Preclinical Medicine, Wannan Medical College, Wuhu 241001, China.
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4
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Ramadan F, Saab R, Hussein N, Clézardin P, Cohen PA, Ghayad SE. Non-coding RNA in rhabdomyosarcoma progression and metastasis. Front Oncol 2022; 12:971174. [PMID: 36033507 PMCID: PMC9403786 DOI: 10.3389/fonc.2022.971174] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 07/25/2022] [Indexed: 12/12/2022] Open
Abstract
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma of skeletal muscle differentiation, with a predominant occurrence in children and adolescents. One of the major challenges facing treatment success is the presence of metastatic disease at the time of diagnosis, commonly associated with the more aggressive fusion-positive subtype. Non-coding RNA (ncRNA) can regulate gene transcription and translation, and their dysregulation has been associated with cancer development and progression. MicroRNA (miRNA) are short non-coding nucleic acid sequences involved in the regulation of gene expression that act by targeting messenger RNA (mRNA), and their aberrant expression has been associated with both RMS initiation and progression. Other ncRNA including long non-coding RNA (lncRNA), circular RNA (circRNA) and ribosomal RNA (rRNA) have also been associated with RMS revealing important mechanistic roles in RMS biology, but these studies are still limited and require further investigation. In this review, we discuss the established roles of ncRNA in RMS differentiation, growth and progression, highlighting their potential use in RMS prognosis, as therapeutic agents or as targets of treatment.
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Affiliation(s)
- Farah Ramadan
- Department of Biology, Faculty of Science II, Lebanese University, Beirut, Lebanon
- Université Claude Bernard Lyon 1, Lyon, France
- INSERM, Unit 1033, LYOS, Lyon, France
- Department of Chemistry and Biochemistry, Laboratory of Cancer Biology and Molecular Immunology, Faculty of Science I, Lebanese University, Hadat, Lebanon
| | - Raya Saab
- Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Department of Pediatric and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Nader Hussein
- Department of Chemistry and Biochemistry, Laboratory of Cancer Biology and Molecular Immunology, Faculty of Science I, Lebanese University, Hadat, Lebanon
| | - Philippe Clézardin
- Université Claude Bernard Lyon 1, Lyon, France
- INSERM, Unit 1033, LYOS, Lyon, France
| | - Pascale A. Cohen
- Université Claude Bernard Lyon 1, Lyon, France
- INSERM, Unit 1033, LYOS, Lyon, France
| | - Sandra E. Ghayad
- Department of Biology, Faculty of Science II, Lebanese University, Beirut, Lebanon
- Aix-Marseille University, INSERM 1263, INRAE 1260, C2VN, Marseille, France
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5
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Liu Y, Ao X, Ji G, Zhang Y, Yu W, Wang J. Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer. Front Oncol 2021; 11:768918. [PMID: 34912714 PMCID: PMC8667691 DOI: 10.3389/fonc.2021.768918] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/15/2021] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors of digestive systems worldwide, with high recurrence and mortality. Chemotherapy is still the standard treatment option for GC and can effectively improve the survival and life quality of GC patients. However, with the emergence of drug resistance, the clinical application of chemotherapeutic agents has been seriously restricted in GC patients. Although the mechanisms of drug resistance have been broadly investigated, they are still largely unknown. MicroRNAs (miRNAs) are a large group of small non-coding RNAs (ncRNAs) widely involved in the occurrence and progression of many cancer types, including GC. An increasing amount of evidence suggests that miRNAs may play crucial roles in the development of drug resistance by regulating some drug resistance-related proteins as well as gene expression. Some also exhibit great potential as novel biomarkers for predicting drug response to chemotherapy and therapeutic targets for GC patients. In this review, we systematically summarize recent advances in miRNAs and focus on their molecular mechanisms in the development of drug resistance in GC progression. We also highlight the potential of drug resistance-related miRNAs as biomarkers and therapeutic targets for GC patients.
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Affiliation(s)
- Ying Liu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, China.,School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Xiang Ao
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Guoqiang Ji
- Clinical Laboratory, Linqu People's Hospital, Linqu, China
| | - Yuan Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Wanpeng Yu
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Jianxun Wang
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
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6
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Busch M, Miroschnikov N, Dankert JT, Wiesehöfer M, Metz K, Stephan H, Dünker N. Impact of RARα and miR-138 on retinoblastoma etoposide resistance. Tumour Biol 2021; 43:11-26. [PMID: 33935126 DOI: 10.3233/tub-200072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.
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Affiliation(s)
- Maike Busch
- Institute of Anatomy II, Department of Neuroanatomy, University of Duisburg-Essen, Medical Faculty, Essen, Germany
| | - Natalia Miroschnikov
- Institute of Anatomy II, Department of Neuroanatomy, University of Duisburg-Essen, Medical Faculty, Essen, Germany
| | | | - Marc Wiesehöfer
- Institute of Anatomy, University of Duisburg-Essen, Medical Faculty, Essen, Germany
| | - Klaus Metz
- Institute of Pathology, University of Duisburg-Essen, Medical Faculty, Essen, Germany
| | - Harald Stephan
- Division of Haematology and Oncology, Children's Hospital, University of Duisburg-Essen, Essen, Germany
| | - Nicole Dünker
- Institute of Anatomy II, Department of Neuroanatomy, University of Duisburg-Essen, Medical Faculty, Essen, Germany
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Abstract
PURPOSE Esophageal squamous cell carcinoma (ESCC) is one of the predominant types of esophageal cancer with poor prognosis which shows high prevalence in eastern countries. Studying microRNAs that were considered for their capabilities such as tissue-specific expression and involvement in different cell features may be informative in the field of diagnostic and prognostic tumor markers. The expression levels of miR-27a and miR-24-2 have been reported to be dysregulated in various cancers and contribute in tumorigenesis and progression; thus, evaluating their expressional behavior and its association with tumor states alteration in ESCC could potentially be helpful. METHODS The study was conducted on 30 fresh specimens including tumor and normal counterparts' tissues of ESCC. After the extraction of total RNA, complementary DNA synthesis was performed by the use of linear specific primers. Eventually, real-time polymerase chain reaction was carried out for the measurement of microRNAs expression level. RESULTS According to the obtained data, miR 27a and miR-24-2 were significantly upregulated (~2.5 fold, p < 0.05) in tumor specimens compared with their normal adjacent tissue; Moreover, upregulation of miR-27a and 24-2 showed cooperative relationship while analyzed. However, there was no correlation between clinicopathological features and microRNAs upregulation. CONCLUSIONS The results of this study show that miR-27a and miR-24-2 cooperatively upregulate in ESCC and suggest that these microRNAs can be introduced as a candidate for further study in the field of screening and prognostic biomarkers.
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8
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Peng Q, Zhao P, Shen Y, Cheng M, Wu Y, Zhu Y. Prognostic implication and functional exploration for microRNA-20a as a molecular biomarker of gastrointestinal cancer. BMC Cancer 2020; 20:420. [PMID: 32410584 PMCID: PMC7227208 DOI: 10.1186/s12885-020-06875-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 04/16/2020] [Indexed: 02/07/2023] Open
Abstract
Background It is generally accepted that microRNA-20a (miR-20a) is aberrantly expressed in gastrointestinal cancer (GIC), and may be associated with the prognosis of GIC patients. Nevertheless, the clinical prognostic value of miR-20a expression in GIC remains controversial. Methods We first conducted a comprehensive literature search of the clinical data and pooled them for evidence in assessing prognostic significance of miR-20a expression in GIC. Afterwards, we applied some bioinformatic analysis methods to explore the biological function of miR-20a and explain why miR-20a could act as an effective biomarker. Results The pooled results showed that enhanced miR-20a expression was significantly associated with poor survival in GIC patients (HR: 1.36; 95%CI: 1.21–1.52; P < 0.001). According to the subgroup analysis, the ethnicity, cancer type, sample source, and sample size may have an impact on the predictive roles for miR-20a. The gene ontologies enriched by the predicted miR-20a targets were highly associated with some important biological processes, cell components and molecular functions. Moreover, a series of prominent pathways linked with GIC carcinogenesis were identified. Ultimately, the crucial targets and modules were identified by constructing the protein-protein interaction network of miR-20a targets, which were highly associated with the initiation and progression of GIC according to previous molecular biology experiments. Conclusions Our results indicated that high expression of miR-20a may be a credible indicator of worse prognosis in GIC. Further studies involving biological experiments and larger sample sizes should be performed to validate these findings.
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Affiliation(s)
- Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Peifeng Zhao
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yi Shen
- Department of Radiation Oncology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Ming Cheng
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yongyou Wu
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
| | - Yaqun Zhu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China. .,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
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9
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Deng Z, Wu J, Xu S, Chen F, Zhang Z, Jin A, Wang J. Exosomes-microRNAs interacted with gastric cancer and its microenvironment: a mini literature review. Biomark Med 2020; 14:141-150. [PMID: 32064893 DOI: 10.2217/bmm-2019-0387] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Exosomes have appeared as fundamental vehicle-modulated crosstalk among various cells in the tumor microenvironment. The systematic understanding of exosomes in gastric cancer (GC) enhances our comprehension about the tumor growth, metastasis, chemoresistance and diagnosis of cancers. The versatile functions of exosomes provide reasonable explanations about the propensity for GC metastasis. The selectively enriched components, especially some exosomal miRNAs, are potential noninvasive biomarkers for sensitive and specific GC diagnosis. Given the characteristics of exosomes, frontier researchers are stimulated to modulate the biogenesis, concentrations or release of exosomes so as to disturb malignant signals between cells. Abnormal expression profiles of exosomal miRNAs afford potential GC therapeutic or diagnostic strategies in future.
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Affiliation(s)
- Zhiyong Deng
- The BioBank, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
| | - Jianhong Wu
- The Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
| | - Song Xu
- The Department of Pathology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
| | - Fang Chen
- The Department of Pathology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
| | - Zhiqing Zhang
- The BioBank, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
| | - Anqi Jin
- The BioBank, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
| | - Jianjun Wang
- The Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, People's Republic of China
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10
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Li K, Zhu X, Chen X, Wang X. MicroRNA‑27a‑3p promotes epithelial‑mesenchymal transition by targeting NOVA alternative splicing regulator 1 in gastric cancer. Mol Med Rep 2020; 21:1615-1622. [PMID: 32016460 DOI: 10.3892/mmr.2020.10949] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 06/22/2019] [Indexed: 11/05/2022] Open
Abstract
NOVA alternative splicing regulator 1 (NOVA1) dysregulation has been detected in the gastric cancer microenvironment. Decreased NOVA1 expression has been linked to the progression and poor prognosis of gastric cancer; however, the role of NOVA1 in regulating epithelial‑mesenchymal transition (EMT) remains unclear in this disease. Experimental evidence has shown that miR‑27a‑3p is a potential oncogene in gastric cancer. In the present study, we observed that miR‑27a‑3p expression was increased in gastric cancer and was inversely associated with overall survival. Overexpression of miR‑27a‑3p promoted EMT in AGS gastric cancer cells. Additionally, overexpression of miR‑27a‑3p inhibited NOVA1 expression, while silencing of NOVA1 promoted EMT in AGS cells. A total of 108 gastric cancer samples were examined for NOVA1 expression by immunohistochemistry. Decreased NOVA1 expression was linked to lymph node metastasis, tumor‑node‑metastasis stage and shorter overall survival. Therefore, these results indicated that NOVA1 could be a potential tumor suppressive gene and that miR‑27a‑3p promotes EMT by targeting NOVA1 in gastric cancer.
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Affiliation(s)
- Kai Li
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Xiangrong Zhu
- Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China
| | - Xihua Chen
- Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China
| | - Xiongtie Wang
- Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China
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11
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Gao Y, Xi H, Wei B, Cui J, Zhang K, Li H, Cai A, Shen W, Li J, Rosell R, Chao J, Chen T, Klempner S, Qiao Z, Chen L. Association Between Liquid Biopsy and Prognosis of Gastric Cancer Patients: A Systematic Review and Meta-Analysis. Front Oncol 2019; 9:1222. [PMID: 31850190 PMCID: PMC6901923 DOI: 10.3389/fonc.2019.01222] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 10/25/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Reports regarding liquid biopsy and gastric cancer (GC) have emerged rapidly in recent decades, yet their prognostic value still remains controversial. This study was aimed to assess the impact of liquid biopsy, including circulating tumor cells (CTCs) and cell-free nucleic acids, on GC patients' prognosis. Methods: PubMed, Medline, EMBASE, and ClinicalTrial.gov databases were searched for studies that report GC patient survival data stratified by CTC/circulating tumor DNA (ctDNA)/circulating miRNAs' status. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for patients' overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were recorded or calculated depending on circulating target status. Results: We initially identified 4,221 studies, from which 43 were eligible for further analysis, comprising 3,814 GC patients. Pooled analyses showed that detection of certain CTCs, ctDNA, and circulating miRNA was associated with poorer OS (CTCs: HR = 1.84, 95%CI 1.50–2.26, p < 0.001; ctDNA: HR = 1.78, 95%CI 1.36–2.34, p < 0.001; circulating miRNA: HR = 1.74, 95%CI 1.13–2.69, p < 0.001) and DFS/PFS (CTCs: HR = 3.39, 95%CI 2.21–5.20, p < 0.001; ctDNA: HR = 2.38, 95%CI 1.31–4.32, p = 0.004; circulating miRNA: HR = 3.30, 95%CI 2.39–4.55, p < 0.001) of GC patients, regardless of disease stage and time point at which sample is taken (at baseline or post-treatment). Conclusions: The presence of CTCs and/or cellular components identifies a group of GC with poorer prognosis. Among circulating markers, CTCs demonstrated a stronger and more stable predictive value for late-stage disease and among Mongolian populations with GC. Less data are available for ctDNA and miRNA; however, their presence may also reflect aggressive biology and warrants further prospective study.
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Affiliation(s)
- Yunhe Gao
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China.,General Surgery Institute, Chinese PLA General Hospital, Beijing, China
| | - Hongqing Xi
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Bo Wei
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China.,General Surgery Institute, Chinese PLA General Hospital, Beijing, China
| | - Jianxin Cui
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Kecheng Zhang
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Hua Li
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Aizhen Cai
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China.,General Surgery Institute, Chinese PLA General Hospital, Beijing, China
| | - Weishen Shen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China.,Nanjing General Hospital of Nanjing Military Command, Nanjing, China
| | - Jiyang Li
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China.,General Surgery Institute, Chinese PLA General Hospital, Beijing, China
| | - Rafael Rosell
- Catalan Institute of Oncology, Germans Trias i Pujol Health Science Institute and Hospital, Barcelona, Spain
| | - Joseph Chao
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United States
| | - Tianhui Chen
- Department of Cancer Prevention, Institute of Cancer and Basic Medicine (ICBM), Zhejiang Provincial Office for Cancer Prevention and Control, Cancer Hospital of the University of CAS, Chinese Academy of Sciences (CAS), Hangzhou, China
| | - Samuel Klempner
- The Angeles Clinic and Research Institute, Los Angeles, CA, United States.,Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Zhi Qiao
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Lin Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China.,General Surgery Institute, Chinese PLA General Hospital, Beijing, China
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12
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Zhang J, Cao Z, Yang G, You L, Zhang T, Zhao Y. MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations. Front Oncol 2019; 9:893. [PMID: 31572683 PMCID: PMC6751266 DOI: 10.3389/fonc.2019.00893] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 08/27/2019] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRNAs) are a family of highly conserved, non-coding single-stranded RNAs transcribed as ~70 nucleotide precursors to an 18–22 nucleotide product (1). miRNAs can silence their homologous target genes at the post-transcriptional level, and these genes have been revealed to play an important role in tumorigenesis, invasion and metastasis (2). MicroRNA-27a (miR-27a), transcripted by miR-27a gene, has proved to implicate with many kinds of solid tumors, showing potential as a useful biomarker or drug target for clinical application. However, even though miR-27a has been reported in many cancers, the mechanism and signal pathways of miR-27 in oncogenesis, invasion, and metastasis are still obscure. Moreover, recent studies show that miR-27a pays an important role in epithelial-mesenchymal-transition, regulating tumor immune response, and chemoresistance. In this review, we summarize the current literature, demonstrate the established link between miR-27a and tumorigenesis, and focus on recently identified mechanisms. The review also aims to demonstrate the potential of miR-27a as a diagnostic and/or prognostic biomarker in solid tumors and to discuss the possibilities of targeted therapy and drug design.
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Affiliation(s)
- Jingcheng Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhe Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gang Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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13
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Zhang Y, Yang C, Yang S, Guo Z. MiRNA‐27a decreases ultraviolet B irradiation‐induced cell damage. J Cell Biochem 2019; 121:1032-1038. [PMID: 31452277 DOI: 10.1002/jcb.29337] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 07/15/2019] [Indexed: 12/17/2022]
Affiliation(s)
- YuanJing Zhang
- Department of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei China
| | - ChunJun Yang
- Department of Dermatology the Second Affiliated Hospital of Anhui Medical University Hefei China
| | - Sen Yang
- Department of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei China
| | - Ze Guo
- Department of Dermatology the First Affiliated Hospital of Anhui Medical University Hefei China
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14
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Moradi Marjaneh R, Khazaei M, Ferns GA, Avan A, Aghaee-Bakhtiari SH. MicroRNAs as potential therapeutic targets to predict responses to oxaliplatin in colorectal cancer: From basic evidence to therapeutic implication. IUBMB Life 2019; 71:1428-1441. [PMID: 31322820 DOI: 10.1002/iub.2108] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Accepted: 05/31/2019] [Indexed: 12/28/2022]
Abstract
Colorectal cancer (CRC) is one of the most common malignancies with poor prognosis. Oxaliplatin-based chemotherapy is an important treatment for CRC; however, the cells develop resistance to therapy. The mechanisms underlying oxaliplatin resistance are complex and unclear. There is increasing evidence that microRNAs (miRNAs) (i.e., miR-34a, miR-143, miR-153, miR-27a, miR-218, and miR-520) play an essential role in tumorigenesis and chemotherapy resistance, by targeting various cellular and molecular pathways (i.e., PI3K/Akt/Wnt, EMT, p53, p21, and ATM) that are involved in the pathogenesis of CRC. Identifying the miRNAs that are involved in chemo-resistance, and their function, may help as a potential therapeutic option for treatment of CRC or as potential prognostic biomarker. Here, we summarized the clinical impact of miRNAs that have critical roles in the development of resistance to oxaliplatin in CRC.
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Affiliation(s)
- Reyhaneh Moradi Marjaneh
- Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.,Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Department of Medical Education, Brighton and Sussex Medical School, Perso Falmer, Brighton, United Kingdom
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Hamid Aghaee-Bakhtiari
- Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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15
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Cui M, Yao X, Lin Y, Zhang D, Cui R, Zhang X. Interactive functions of microRNAs in the miR-23a-27a-24-2 cluster and the potential for targeted therapy in cancer. J Cell Physiol 2019; 235:6-16. [PMID: 31192453 DOI: 10.1002/jcp.28958] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/23/2019] [Accepted: 05/24/2019] [Indexed: 12/18/2022]
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs about 19-22 nucleotides in length. Growing evidence has reported the significant role of miRNAs in various cancer-associated biological processes, such as proliferation, differentiation, apoptosis, metabolism, invasion, metastasis, and drug resistance. However, most studies focus on the targets of some individual miRNAs; the interactive and global functions of diverse miRNAs are still unclear and the phenomenon of the gathering of miRNAs in clusters has always been ignored. On the other hand, the fact that a single miRNA may regulate many genes and that numerous mRNAs are regulated by the same miRNA also makes it imperative to further study the cooperating characteristics of miRNAs in cancer. MiR-23a-27a-24-2 is located in the human chromosome 9q22, forming three mature miRNAs: miR-23a, miR27a, and miR-24, which are expressed abnormally in many malignant tumors. This review aims to summarize the interactive functions of miRNAs in miR-23a-27a-24-2 clusters in cancer from the perspectives of the regulation network, tumor microenvironment, and targeted therapy.
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Affiliation(s)
- Mengying Cui
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, P. R. China
| | - Xiaoxiao Yao
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, P. R. China
| | - Yang Lin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, P. R. China
| | - Dan Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, P. R. China
| | - Ranji Cui
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, P. R. China
| | - Xuewen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, P. R. China
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16
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Li X, Xu M, Ding L, Tang J. MiR-27a: A Novel Biomarker and Potential Therapeutic Target in Tumors. J Cancer 2019; 10:2836-2848. [PMID: 31258791 PMCID: PMC6584939 DOI: 10.7150/jca.31361] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 05/09/2019] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are endogenous, time sequencing, conserved and small non-coding RNA molecules (19-25 bp long) that regulate gene expression at the post-transcriptional level by binding to the partial sequence homology of the 3'-untranslated region of target messenger (m)RNA. The miRNA-27 family consists of miR-27a and miR-27b, which are transcribed from different chromosomes and different in nucleotide at the 3' end. It has been reported that miR-27a was located on chromosome 19 and played a vital role in tumor development. Increasing evidences support a vital role for miR-27a in modulating polymorphisms, tumorigenesis, proliferation, apoptosis, invasion, migration and angiogenesis. Apart from it, miR-27a could affect drug sensitivity, treatment of cancer and patients prognosis. The miR-27a could be an oncogene or a tumor suppressor in several types of cancer, including colon cancer, pancreatic cancer, breast cancer, bladder cancer and hepatocellular carcinoma. In this review, we discuss the role of miR-27a in tumor biology and clinical significance in detail and offer novel insights into molecular targeting therapy for human cancers.
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Affiliation(s)
- Xingwang Li
- School of Clinical Medicine, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China
| | - Min Xu
- School of Clinical Medicine, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China
| | - Li Ding
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China
| | - Jinhai Tang
- School of Clinical Medicine, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.,Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China
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17
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Yun X, Bai Y, Li Z, Wang D, Zhu Y, Jing C. rs895819 in microRNA-27a increase stomach neoplasms risk in China: A meta-analysis. Gene 2019; 707:103-108. [PMID: 31054359 DOI: 10.1016/j.gene.2019.04.061] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/19/2019] [Accepted: 04/22/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Across the globe, gastric cancer is a significant public health problem. This meta-analysis was conducted to investigate the association of microRNA-27a (miRNA-27a) rs895819 with gastric cancer risk. METHODS The search of databases updated on October 10, 2018 included Pubmed, Embase, Cochrane Library and Web of science. Odds ratio (ORs) and 95% confidence interval (CIs) were calculated to assess the risk of tumor. RESULTS Overall meta-analysis suggested the miRNA-27a rs895819 was not related to the gastric carcinogenesis among all model including allele contrast (G vs A, pooled OR: 1.096, 95% CI: 0.962-1.249, P = 0.196), codominant model (GG vs AA, pooled OR: 1.124, 95% CI: 0.794-1.592, P = 0.590; AG vs AA, pooled OR: 1.101, 95% CI: 0.966-1.217, P = 0.060), dominant model (AG + GG vs AA, pooled OR: 1.123, 95% CI: 0.964-1.307, P = 0.136) and recessive model (GG vs AG + AA, pooled OR: 0.927, 95% CI: 0.673-1.278, P = 0.644). Interestingly, among different ethnicity group, significant relation between rs895819 and gastric cancer was observed in co-dominant model among Chinese population (AG vs AA, pooled OR: 1.158, 95% CI: 1.038-1.291, P = 0.008) but not some regions of European population (AG vs AA, pooled OR: 0.852, 95% CI: 0.632-1.148, P = 0.179). CONCLUSIONS Our results find that rs895819 contributed to occurrence of gastric cancer in co-dominant model in Chinese population.
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Affiliation(s)
- Xiaojing Yun
- The Second People's Hospital of Liaocheng, Linqing, Shandong Province 252600, PR China
| | - Yuhuan Bai
- The Second People's Hospital of Liaocheng, Linqing, Shandong Province 252600, PR China
| | - Zhihui Li
- The Second People's Hospital of Liaocheng, Linqing, Shandong Province 252600, PR China
| | - Dongmei Wang
- The Second People's Hospital of Liaocheng, Linqing, Shandong Province 252600, PR China
| | - Yusen Zhu
- The Second People's Hospital of Liaocheng, Linqing, Shandong Province 252600, PR China
| | - Changchun Jing
- The Second People's Hospital of Liaocheng, Linqing, Shandong Province 252600, PR China.
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18
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Chen C, Tang X, Liu Y, Zhu J, Liu J. Induction/reversal of drug resistance in gastric cancer by non-coding RNAs (Review). Int J Oncol 2019; 54:1511-1524. [PMID: 30896792 PMCID: PMC6438417 DOI: 10.3892/ijo.2019.4751] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/21/2019] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer (GC) is one of the most prevalent and malignant types of cancer worldwide. In China, it is the second most common type of cancer and the malignancy with the highest incidence and mortality rate. Chemotherapy for GC is not always effective due to the development of drug resistance. Drug resistance, which is frequently observed in GC, undermines the success rate of chemotherapy and the survival of patients with GC. The dysregulation of non‑coding RNAs (ncRNAs), primarily microRNAs (miRNAs or miRs) and long non‑coding RNAs (lncRNAs), is involved in the development of GC drug resistance via numerous mechanisms. These mechanisms contribute to the involvement of a large and complex network of ncRNAs in drug resistance. In this review, we focus on and summarize the latest research on the specific mechanisms of action of miRNAs and lncRNAs that modulate drug resistance in GC. In addition, we discuss future prospects and clinical applications of ncRNAs as potential targeted therapies against the chemoresistance of GC.
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Affiliation(s)
- Chao Chen
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Xiaohuan Tang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Yuanda Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jiaming Zhu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jingjing Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
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19
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Huang D, Peng Y, Ma K, Deng X, Tang L, Jing D, Shao Z. MiR-20a, a novel promising biomarker to predict prognosis in human cancer: a meta-analysis. BMC Cancer 2018; 18:1189. [PMID: 30497428 PMCID: PMC6267918 DOI: 10.1186/s12885-018-4907-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Accepted: 10/08/2018] [Indexed: 02/09/2023] Open
Abstract
Background Recently, microRNA-20a (miR-20a) has been reported to influence the clinical features and may have prognostic value in human cancers. The present meta-analysis assessed the prognostic role of miR-20a in various carcinomas. Methods Literature searches of seven electronic databases were performed for eligible articles of the prognostic role of miR-20a in human cancers. Hazard ratios (HR) for overall survival (OS), disease free survival (DFS), progression-free survival (PFS) as well as their 95% confidence intervals (95%CIs) were used to assess the influence of miR-20a expression on patient prognosis. Odds ratio (OR) and 95%CIs were applied to evaluate the correlation between miR-20a expression and clinicopathological characteristics. Results Based on the OS analyzed by log rank tests, there was a significant association between miR-20a levels and OS by fixed effects model. By subgroup analyses, the significance was also observed in the studies of specimen derived from blood and gastrointestinal cancer group. The independent prognostic role of miR-20a expression for the OS was observed significantly by fixed effects model. In addition, we observed significant association between miR-20a expression levels and DFS of log rank tests, DFS of cox regression. Significant relation of gender/differentiation and the expression level of miR-20a was identified. Conclusions Base on the findings, the elevated miR-20a expression level is related to poor prognosis of gastrointestinal cancer patients. As for other types of carcinomas, the results are still not stable and more studies are required to further identify miR-20a prognostic values. In addition, miR-20a expression level is relatively higher in women than that in men, and increased miR-20a expression level is linked to poor tumor differentiation.
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Affiliation(s)
- Donghua Huang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yizhong Peng
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kaige Ma
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiangyu Deng
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Lu Tang
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Doudou Jing
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zengwu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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20
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Wang F, Sun Y. Overexpression of Myosin Phosphatase Target Subunit 1 (MYPT1) Inhibits Tumor Progression and Metastasis of Gastric Cancer. Med Sci Monit 2018; 24:2508-2517. [PMID: 29687789 PMCID: PMC5937360 DOI: 10.12659/msm.906852] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Myosin phosphatase target subunit 1 (MYPT1) serves as a subgroup of myosin phosphatases, and is frequently low-expressed in human cancers. However, little is known about the effects of MYPT1 in gastric cancer (GC). Material/Methods In our study, MYPT1 expression was detected by quantitative real-time reverse transcription PCR (qRT-PCR) in GC tissues, different advanced pathological stages of GC tissues, and preoperative and postoperative patients. Kaplan-Meier analysis was used to measure the overall survival of GC patients. MYPT1 expression was analyzed by qRT-PCR and Western blot assays in GES-1 cells and GC cells. Cell proliferation, cycle, and migration and invasion abilities were detected by CCK-8, flow cytometry, and Transwell assays. E-cadherin, TIMP-2, MMP-2, MMP-9 RhoA, and p-RhoA expressions were assessed by qRT-PCR and Western blot assays in treated SNU-5 cells. Results Our results indicated that MYPT1 was down-regulated in GC tissues and cells, and is related to clinical stages and overall survival of GC. Functional research demonstrated that overexpression of MYPT1 can inhibit cell proliferation, cell cycle progression, and migration and invasion of GC cells. Many studies on mechanisms reported that overexpression of MYPT1 dramatically improved the expression levels of cell cycle-related genes (Cyclin D1 and c-myc), significantly increased epithelial marker (E-cadherin) expression, and decreased invasion-associated genes (TIMP-2 and MMP-2) expressions in SNU-5 cells. In addition, we found that MYPT1 suppressed RhoA phosphorylation. Conclusions We verified that MYPT1 inhibits GC cell proliferation and metastasis by regulating RhoA phosphorylation.
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Affiliation(s)
- Fengyong Wang
- Department of Gastrointestinal and Pancreatic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland)
| | - Yuanshui Sun
- Department of Gastrointestinal and Pancreatic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland)
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21
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Ahrend H, Kaul A, Ziegler S, Brandenburg LO, Zimmermann U, Mustea A, Burchardt M, Ziegler P, Stope MB. MicroRNA-1 and MicroRNA-21 Individually Regulate Cellular Growth of Non-malignant and Malignant Renal Cells. ACTA ACUST UNITED AC 2018; 31:625-630. [PMID: 28652429 DOI: 10.21873/invivo.11103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Revised: 04/24/2017] [Accepted: 04/27/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND/AIM Due to its poor prognosis, it is increasingly necessary to understand the biology of renal cell cancer (RCC). Therefore, we investigated the role of microRNAs miR-1 and miR-21 in the growth of RCC cells compared to that of non-malignant renal cells. MATERIALS AND METHODS Four malignant cell lines (Caki-1, 786-O, RCC4, A498) were examined regarding their cell growth, microRNA and telomerase expression, and were compared to non-malignant RC-124 renal cells. RESULTS Inconsistencies appeared in the panel of RCC cells regarding antiproliferative and proliferative properties of miR-1 and miR-21, respectively. Notably, and most likely due to immortaliziation, non-malignant RC-124 cells exhibited telomerase expression and activity. CONCLUSION miR-1 and miR-21 functionality in cancer progression, particularly in tumor growth, may be more dependent on the individual cellular context and may reflect RCC heterogeneity. Thus, both microRNAs, in combination with other stratifying biomarkers, may be useful in terms of RCC diagnosis, prognosis, or treatment response.
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Affiliation(s)
- Hannes Ahrend
- Department of Urology, University of Medicine Greifswald, Greifswald, Germany
| | - Anne Kaul
- Department of Gynaecology and Obstetrics, University of Medicine Greifswald, Greifswald, Germany
| | - Susanne Ziegler
- Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany
| | | | - Uwe Zimmermann
- Department of Urology, University of Medicine Greifswald, Greifswald, Germany
| | - Alexander Mustea
- Department of Gynaecology and Obstetrics, University of Medicine Greifswald, Greifswald, Germany
| | - Martin Burchardt
- Department of Urology, University of Medicine Greifswald, Greifswald, Germany
| | - Patrick Ziegler
- Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany
| | - Matthias B Stope
- Department of Urology, University of Medicine Greifswald, Greifswald, Germany
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22
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Xie M, Dart DA, Guo T, Xing XF, Cheng XJ, Du H, Jiang WG, Wen XZ, Ji JF. MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer. Gastric Cancer 2018; 21:41-54. [PMID: 28493075 PMCID: PMC5741792 DOI: 10.1007/s10120-017-0721-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 04/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. METHODS We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. RESULTS Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. CONCLUSIONS MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy.
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Affiliation(s)
- Meng Xie
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Dafydd Alwyn Dart
- Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
| | - Ting Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiao-Fang Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiao-Jing Cheng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hong Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wen G Jiang
- Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
| | - Xian-Zi Wen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Jia-Fu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
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23
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Lopez A, Harada K, Mizrak Kaya D, Dong X, Song S, Ajani JA. Liquid biopsies in gastrointestinal malignancies: when is the big day? Expert Rev Anticancer Ther 2017; 18:19-38. [PMID: 29202614 DOI: 10.1080/14737140.2018.1403320] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Anthony Lopez
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Gastroenterology and Hepatology and Inserm U954, Nancy University Hospital, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Kazuto Harada
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Dilsa Mizrak Kaya
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiaochuan Dong
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shumei Song
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A. Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Quan J, Liu S, Dai K, Jin L, He T, Pan X, Lai Y. MicroRNA-23a/24-2/27a as a potential diagnostic biomarker for cancer: A systematic review and meta-analysis. Mol Clin Oncol 2017; 8:159-169. [PMID: 29387410 DOI: 10.3892/mco.2017.1492] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 05/02/2017] [Indexed: 12/28/2022] Open
Abstract
An increasing number of studies have proven that microRNAs play an important role in the occurrence, development and prognosis of various types of cancer. As a vital gene cluster, the microRNA (miR)-23a/24-2/27a cluster may be an important marker for predicting cancer prognosis and tumor progression. A search was conducted through PubMed, Medline and the Cochrane Library to identify studies investigating the association between the miR-23a/24-2/27a cluster and cancer, and the identified related studies were included in the present meta-analysis. The strength of the association was assessed by hazard ratio (HR) and its 95% confidence interval (95% CI). A total of 21 studies were included in this meta-analysis. The results indicated that a high level of miR-23a exerted a significant effect on overall survival (OS) (HR=2.33, 95% CI: 1.18-4.58; P=0.014), but not on disease-free survival (DFS)/recurrence-free survival (RFS) (HR=1.13, 95% CI: 0.37-3.44; P=0.836). There was an obvious statistically significant association between OS and the expression of miR-24 (HR=2.49, 95% CI: 1.84-3.37; P=0.000), particularly in the digestive system (pooled HR=2.99, 95% CI: 2.17-4.13, P=0.000). In addition, the result suggested a statistically significant association between the expression of miR-27a and OS (pooled HR=1.89, 95% CI: 1.32-2.69; P=0.001), as well as DFS/RFS/progression-free survival (HR=2.19, 95% CI: 1.29-3.70; P=0.003), particularly in renal cell carcinoma (HR=2.30, 95% CI: 1.16-4.67; P=0.017). A subgroup analysis by ethnicity, cancer type and statistical methodology was performed. There was no obvious publication bias. In conclusion, the present study demonstrated that the miR-23a/24-2/27a cluster may be a useful marker for predicting cancer prognosis and tumor progression.
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Affiliation(s)
- Jing Quan
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.,Department of Urology, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Suyue Liu
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.,Department of Thoracic Surgery, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Kangfu Dai
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.,Department of Hepatobiliary Endoscopic Surgery, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Lu Jin
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.,Department of Urology, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Tao He
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.,Department of Urology, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
| | - Xiang Pan
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.,Department of Urology, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Yongqing Lai
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
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Yang W, Ma J, Zhou W, Cao B, Zhou X, Yang Z, Zhang H, Zhao Q, Fan D, Hong L. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer. Expert Opin Ther Targets 2017; 21:1063-1075. [PMID: 28994330 DOI: 10.1080/14728222.2017.1389900] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.
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Affiliation(s)
- Wanli Yang
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Jiaojiao Ma
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Wei Zhou
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Bo Cao
- b The First Brigade of Student , Fourth Military Medical University , Xi'an , China
| | - Xin Zhou
- b The First Brigade of Student , Fourth Military Medical University , Xi'an , China
| | - Zhiping Yang
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Hongwei Zhang
- c Department of Digestive Surgery, Xijing Hospital , Fourth Military Medical University , Xi'an , China
| | - Qingchuan Zhao
- c Department of Digestive Surgery, Xijing Hospital , Fourth Military Medical University , Xi'an , China
| | | | - Liu Hong
- a State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
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Xia L, Yin Z, Li X, Ren Y, Zhang H, Zhao Y, Zhou B. Genetic polymorphisms in pre-miRNAs predict the survival of non-small-cell lung cancer in Chinese population: a cohort study and a meta-analysis. Oncotarget 2017; 8:77963-77974. [PMID: 29100439 PMCID: PMC5652828 DOI: 10.18632/oncotarget.20276] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 07/25/2017] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND To explore the association of genetic polymorphisms in pre-miRNA 30c-1 rs928508 and pre-miRNA 27a rs895819 with non-small-cell lung cancer prognosis. MATERIALS AND METHODS 480 patients from five hospitals were enrolled in this prospective cohort study. They were followed up for five years. The association between genotypes and overall survival was assessed by Cox proportional hazards regression models. A meta-analysis was conducted to provide evidence for the effect of microRNA 27a rs895819 on cancer survival. RESULTS G-allele containing genotypes of microRNA 30c-1 polymorphisms and C-allele containing genotypes of microRNA 27a were significantly associated with poorer overall survival. Multivariate Cox regression models indicated that these genetic polymorhpisms were independently predictive factors of poorer overall survival. In stratified analysis, the effect was observed in many strata. The significant joint effect was also observed in our study. Patients with G allele of microRNA 30c-1 rs928508 and C allele of microRNA 27a rs895819 had the poorer overall survival than patients with C allele of rs928508 and T allele of rs895819. The effect of the microRNA 27a rs895819 on non-small cell lung cancer overall survival was supported by the meta-analysis results. CONCLUSIONS The two single nucleotide polymorphisms in microRNA 30c-1 and microRNA 27a can predict the outcome of non-small cell lung cancer patients and they may decrease the sensitivity to anti-cancer drugs.
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Affiliation(s)
- Lingzi Xia
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, P.R. China
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, 110122, P.R. China
| | - Zhihua Yin
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, P.R. China
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, 110122, P.R. China
| | - Xuelian Li
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, P.R. China
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, 110122, P.R. China
| | - Yangwu Ren
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, P.R. China
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, 110122, P.R. China
| | - Haibo Zhang
- Department of Radiotherapy, Shenyang North Hospital, Shenyang, Liaoning, 110001, P.R. China
| | - Yuxia Zhao
- Department of Radiotherapy Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, P.R. China
| | - Baosen Zhou
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, P.R. China
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, 110122, P.R. China
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Zhang Y, Guan DH, Bi RX, Xie J, Yang CH, Jiang YH. Prognostic value of microRNAs in gastric cancer: a meta-analysis. Oncotarget 2017; 8:55489-55510. [PMID: 28903436 PMCID: PMC5589675 DOI: 10.18632/oncotarget.18590] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 05/08/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Previous articles have reported that expression levels of microRNAs (miRNAs) are associated with survival time of patients with gastric cancer (GC). A systematic review and meta-analysis was performed to study the outcome of it. DESIGN Meta-analysis. METHODS English studies estimating expression levels of miRNAs with any of survival curves in GC were identified up till March 19, 2017 through performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two authors independently. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS). RESULTS Sixty-nine relevant articles about 26 miRNAs with 6148 patients were ultimately included. GC patients with high expression of miR-20b (HR=2.38, 95%CI=1.16-4.87), 21 (HR=1.77, 95%CI=1.01-3.08), 106b (HR=1.84, 95%CI=1.15-2.94), 196a (HR=2.66, 95%CI=1.94-3.63), 196b (HR=1.67, 95%CI=1.38-2.02), 214 (HR=1.84, 95%CI=1.27-2.67) or low expression of miR-125a (HR=2.06, 95%CI=1.26-3.37), 137 (HR=3.21, 95%CI=1.68-6.13), 141 (HR=2.47, 95%CI=1.34-4.56), 145 (HR=1.62, 95%CI=1.07-2.46), 146a (HR=2.60, 95%CI=1.63-4.13), 206 (HR=2.85, 95%CI=1.73-4.70), 218 (HR=2.61, 95%CI=1.74-3.92), 451 (HR=1.73, 95%CI=1.19-2.52), 486-5p (HR=2.45, 95%CI=1.65-3.65), 506 (HR=2.07, 95%CI=1.33-3.23) have significantly poor OS (P<0.05). CONCLUSIONS In summary, miR-20b, 21, 106b, 125a, 137, 141, 145, 146a, 196a, 196b, 206, 214, 218, 451, 486-5p and 506 demonstrate significantly prognostic value. Among them, miR-20b, 125a, 137, 141, 146a, 196a, 206, 218, 486-5p and 506 are strong biomarkers of prognosis in GC.
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Affiliation(s)
- Yue Zhang
- 1 First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, People's Republic of China
| | - Dong-Hui Guan
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Rong-Xiu Bi
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Jin Xie
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Chuan-Hua Yang
- 3 Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Yue-Hua Jiang
- 4 Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
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Zheng Q, Chen C, Guan H, Kang W, Yu C. Prognostic role of microRNAs in human gastrointestinal cancer: A systematic review and meta-analysis. Oncotarget 2017; 8:46611-46623. [PMID: 28402940 PMCID: PMC5542297 DOI: 10.18632/oncotarget.16679] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 03/09/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Gastrointestinal cancers (GICs) mainly including esophageal, gastric and colorectal cancer, are the most common cause of cancer-related death and lead into high mortality worldwide. We performed this systematic review and meta-analysis to elucidate relationship between multiple microRNAs (miRs) expression and survival of GIC patients. METHODS We searched a wide range of database. Fixed-effects and random-effects models were used to calculate the pooled hazard ratio values of overall survival and disease free survival. In addition, funnel plots were used to qualitatively analyze the publication bias and verified by Begg's test while it seems asymmetry. RESULTS 60 studies involving a total of 6225 patients (1271 with esophageal cancer, 3467 with gastric cancer and 1517 with colorectal cancer) were included in our meta-analysis. The pooled hazard ratio values of overall survival related to different miRs expression in esophageal, gastric, colorectal and gastrointestinal cancer were 2.10 (1.78-2.49), 2.02 (1.83-2.23), 2.54 (2.14-3.02) and 2.15 (1.99-2.31), respectively. We have identified a total of 59 miRs including 23 significantly up-regulated expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, etc.) and 36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p, miR-760, miR-206, miR-26a, miR-200b, miR-185, etc.) correlated with poor prognosis in GIC patients. Moreover, 35 of them revealed mechanisms. CONCLUSION Overall, specific miRs are significantly associated with the prognosis of GIC patients and potentially eligible for the prediction of patients survival. It also provides a potential value for clinical decision-making development and may serve as a promising miR-based target therapy waiting for further elucidation.
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Affiliation(s)
- Qiang Zheng
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Changyu Chen
- Department of General Surgery, First Affiliated Hospital of Anhui Traditional Medical University, Hefei, China
| | - Haiyang Guan
- Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China
| | - Weibiao Kang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Changjun Yu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
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Ban JJ, Chung JY, Lee M, Im W, Kim M. MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington's disease. Biochem Biophys Res Commun 2017; 488:316-321. [PMID: 28495533 DOI: 10.1016/j.bbrc.2017.05.040] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 05/07/2017] [Indexed: 01/28/2023]
Abstract
Huntington's disease (HD) is a fatal genetic disease caused by abnormal aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation decreases cell death of the brain and is a promising therapeutic strategy of HD. MicroRNAs are short non-coding nucleotides which modulate various genes and dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs), we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt aggregation. R6/2-derived NSCs can be differentiated under condition of growth factor deprivation, and the progression of differentiation leads to a decrease of MDR-1 level and efflux function of cells. Immunocytochemistry result also confirmed that mHtt aggregation was increased with differentiation. We transfected miR-27a in the R6/2-derived differentiated NSCs, and examined phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can transport mHtt, protein level was increased by miR-27a transfection. Conversely, knock-down of MDR-1 through MDR-1 siRNA increased mHtt aggregation in vitro. Our results indicate that miR-27a could reduce mHtt level of the HD cell by augmenting MDR-1 function.
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Affiliation(s)
- Jae-Jun Ban
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea
| | - Jin-Young Chung
- Department of Veterinary Internal Medicine and Geriatrics, College of Veterinary Medicine, Kangwon National University, Gangwon, South Korea
| | - Mijung Lee
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea
| | - Wooseok Im
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
| | - Manho Kim
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea.
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The Profile of Serum microRNAs Predicts Prognosis for Resected Gastric Cancer Patients Receiving Platinum-Based Chemotherapy. Dig Dis Sci 2017; 62:1223-1234. [PMID: 28341869 DOI: 10.1007/s10620-017-4513-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 02/25/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Adjuvant chemotherapy is an important component in the treatment of gastric cancer (GC) patients; however, some patients do not respond to the drugs. We aimed to develop a practical profile based on serum microRNAs (miRNAs) that can be used to predict patients likely to respond to treatment. METHODS Microarrays were used to screen cisplatin-resistant SGC7901/DDP GC cells and the parental SGC7901 cell lines for miRNAs related to chemotherapy sensitivity. The correlation between the expression patterns of identified serum miRNAs and overall survival was confirmed in 68 GC patients. Furthermore, we also validated the signature of the serum miRNAs in an independent cohort of 50 GC patients. RESULTS From the screening microarrays, we focused on miR-15a, miR-15b and miR-93 as downregulated miRNAs in the SGC7901/DDP cells and miR-27a, miR-106a and miR-664 as upregulated miRNAs. Only serum miR-106, miR-15a, miR-93 and miR-664 were useful in predicting the prognosis of patients who received adjuvant chemotherapy. We identified a signature of four serum miRNAs (miR-106, miR-15a, miR-93 and miR-664) that, when combined, can be used as a risk score for overall survival. Patients with a higher risk score had worse prognosis (p < 0.05). For the independent cohort of patients, the signature of the four miRNAs predicted prognosis well. CONCLUSION Our data showed that the risk score derived from the four serum miRNAs was closely associated with the overall survival in GC patients who received adjuvant chemotherapy.
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Zhang L, Huang Z, Zhang H, Zhu M, Zhu W, Zhou X, Liu P. Prognostic value of candidate microRNAs in gastric cancer: A validation study. Cancer Biomark 2017; 18:221-230. [PMID: 27983528 DOI: 10.3233/cbm-160091] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Studies have reported the prognostic value of dysregulated microRNAs (miRNAs) in gastric cancer (GC). However, the results demonstrated so far are inconsistent. OBJECTIVE To better understand the miRNAs with prognostic relevance. METHODS Evaluable miRNAs were selected based on our selection criteria and further analyzed in formalin-fixed paraffin-embedded (FFPE) tissue samples of 169 GC patients using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS A total of 19 miRNAs were selected as candidate miRNAs. Among those miRNAs identified, high expression of miR-21-5p was related to poor overall survival (OS) and disease free survival (DFS) and was identified as an independent prognostic factor. Cases with high level of miR-200c-3p showed poor DFS. Subgroup analysis revealed that high expression of miR-21-5p and miR-222-3p was associated with poor OS and DFS in GC patients not received adjuvant chemotherapy. In male patients, high expression level of miR-21-5p was related to poor OS and DFS. CONCLUSIONS The present study confirmed that elevated level of miR-21-5p could serve as an independent predictor for poor OS and DFS of GC patients. Moreover, miR-200c-3p, miR-222-3p might also play important roles in the prognosis of GC patients. Further studies are warranted to validate our findings and identify the functions and mechanisms of these miRNAs.
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Li M, Gu K, Liu W, Xie X, Huang X. MicroRNA-200c as a prognostic and sensitivity marker for platinum chemotherapy in advanced gastric cancer. Oncotarget 2017; 8:51190-51199. [PMID: 28881640 PMCID: PMC5584241 DOI: 10.18632/oncotarget.17087] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 03/21/2017] [Indexed: 11/25/2022] Open
Abstract
We examined microRNA-200c (miR-200c) expression in tumor tissues and plasma of patients with advanced gastric cancer and correlated miR-200c expression with treatment efficacy of platinum chemotherapy and patient prognosis. Tumor tissues were collected from 51 patients with advanced gastric cancer who received platinum-containing chemotherapies. The plasma was collected from the same group of patients and 51 subjects with chronic superficial gastritis. Quantitative RT-PCR was used to evaluate miR-200c expression, and its correlation with treatment efficacy and patient prognosis was analyzed. The results showed that the miR-200c expression in gastric cancer tissues and in plasma were significantly lower than tumor-adjacent tissues and in patients with chronic superficial gastritis (both p <0.05). No significant correlation was found between miR-200c expression in tumors or plasma and clinical characteristics. Patients with higher miR-200c expression had better treatment outcomes with platinum chemotherapy and longer progression-free survival and overall survival than patients with lower miR-200c expression. Receiver-operating characteristic curve analysis showed that miR-200c expression in gastric cancer tissues and plasma distinguished patients' treatment outcomes. Multivariate analyses confirmed that over expression of miR-200c both in gastric cancer tissue and plasma is associated with longer progression-free survival and overall survival. Taken together, our study indicated that miR-200c expression in gastric cancer tissues and plasma of patients with advanced gastric cancer is associated with better treatment efficacy and prognosis with platinum chemotherapy, suggesting that expression of miR-200c may be predictive for chemotherapy and prognosis in advanced gastric cancer patients.
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Affiliation(s)
- Min Li
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
| | - Kangsheng Gu
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
| | - Wei Liu
- Department of Oncology, Huaibei People's Hospital, Huaibei, Anhui 235000, P.R. China
| | - Xiaoque Xie
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
| | - Xiaolu Huang
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
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Biersack B. Interactions between anticancer active platinum complexes and non-coding RNAs/microRNAs. Noncoding RNA Res 2017; 2:1-17. [PMID: 30159416 PMCID: PMC6096430 DOI: 10.1016/j.ncrna.2016.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 10/07/2016] [Accepted: 10/07/2016] [Indexed: 12/13/2022] Open
Abstract
Platinum(II) complexes such as cisplatin, carboplatin and oxaliplatin are clinically approved for the therapy of various solid tumors. Challenging pathogenic properties of cancer cells and the response of cancers towards platinum-based drugs are strongly influenced by non-coding small RNA molecules, the microRNAs (miRNAs). Both increased platinum activity and formation of tumor resistance towards platinum drugs are controlled by miRNAs. This review gives an overview of the interactions between platinum-based drugs and miRNAs, and their influence on platinum activity in various cancer types is discussed.
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Key Words
- 5-FU, 5-fluorouracil
- Anticancer drugs
- CBDCA, cyclobutane-1,1-dicarboxylate
- Carboplatin
- Cisplatin
- DACH, 1,2-diaminocyclohexane
- DDP, cisplatin
- EGCG, (−)-epigallocatechin-3-gallate
- EOX, epirubicin/oxaliplatin/xeloda
- FOLFOX, folinate/5-FU/oxaliplatin
- GC, gemcitabine/cisplatin, gastric cancer
- LNA, locked nucleic acid
- MVAC, methotrexate/vinblastine/adriamycin/cisplatin
- MicroRNA
- Oxaliplatin
- Platinum complexes
- XELOX, xeloda/oxaliplatin
- dTTP, deoxythymidine triphosphate
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Abstract
The development of drug resistance has largely limited the clinical outcome of anti-cancer treatment. Recent work has highlighted the involvement of non-coding RNAs, microRNAs (miRNAs), in cancer development. The present study aimed to investigate the role of miR-21 in the development of drug resistance to paclitaxel in gastric cancer cells. Our study found that the expression of miR-21 upregulated in the paclitaxel resistant cell line SGC7901/paclitaxel compared to its parental line SGC7901. Moreover, over-expression of miR-21 significantly decreased antiproliferative effects and apoptosis induced by paclitaxel, while knockdown of miR-21 dramatically increased antiproliferative effects and apoptosis induction by paclitaxel. Moreover, our results demonstrated that miR-21 may modulate the sensitivity to PTX, at least in part, by regulating the expression of P-glycoprotein.
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Abstract
Drug resistance of gastric cancer cells is one of the main reasons that lead to failure of chemotherapy in gastric cancer. Gastric cancer cells can be resistant to chemotherapeutic drugs and targeted drugs, which leads to poor therapeutic effects. Although the mechanisms of drug resistance of gastric cancer cells have long been investigated, no effective drug that can reverse the drug resistance of gastric cancer cells has been found. Therefore, it is important to reverse the drug resistance of gastric cancer cells to improve the prognosis of gastric cancer. In this paper, we review the mechanisms of drug resistance of gastric cancer cells to chemotherapeutic drugs and targeted drugs, summarize current situation for research of drug resistance of gastric cancer cells, and discuss the future development direction in this field.
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Shang Y, Feng B, Zhou L, Ren G, Zhang Z, Fan X, Sun Y, Luo G, Liang J, Wu K, Nie Y, Fan D. The miR27b-CCNG1-P53-miR-508-5p axis regulates multidrug resistance of gastric cancer. Oncotarget 2016; 7:538-49. [PMID: 26623719 PMCID: PMC4808016 DOI: 10.18632/oncotarget.6374] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Accepted: 11/13/2015] [Indexed: 12/24/2022] Open
Abstract
Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among gastric cancer (GC) patients. In a previous study using high-throughput functional screening, we identified 11 microRNAs (miRNAs) that regulate MDR in GC and found that miR-508-5p reversed MDR by targeting ABCB1 and ZNRD1. However, the mechanism by which miR-508-5p was decreased in chemo-resistant GC cells was unclear. In this study, we found that ectopic miR-27b is sufficient to sensitize tumors to chemotherapy in vitro and in vivo. Moreover, miR-27b directly targets the 3′ untranslated regions (3′-UTRs) of CCNG1, a well-known negative regulator of P53 stability. Interestingly, miR-27b up-regulation leads to increased miR-508-5p expression, and this phenomenon is mediated by CCNG1 and P53. Further investigation indicated that miR-508-5p is directly regulated by P53. Thus, the miR-27b/CCNG1/P53/miR-508-5p axis plays important roles in GC-associated MDR. In addition, miR-27b and miR-508-5p expression was detected in GC tissues with different chemo-sensitivities, and we found that tissues in which miR-27b and miR-508-5p are up-regulated are more sensitive to chemotherapy. Together, these data suggest that the combination of miR-27b and miR-508-5p represents a potential marker of MDR. Restoring the miR-27b and miR-508-5p levels might contribute to MDR reversion in future clinical practice.
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Affiliation(s)
- Yulong Shang
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Bin Feng
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Lin Zhou
- The 88th Hospital of PLA, Tai'an 271001, China
| | - Gui Ren
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Zhiyong Zhang
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Xing Fan
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Yi Sun
- Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Guanhong Luo
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Jie Liang
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
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Wang CY, Wang SG, Wang JL, Zhou LY, Liu HJ, Wang YF. Effect of miRNA-27a and Leptin Polymorphisms on Risk of Recurrent Spontaneous Abortion. Med Sci Monit 2016; 22:3514-3522. [PMID: 27694792 PMCID: PMC5049305 DOI: 10.12659/msm.897147] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background The aim of this study was to investigate the possible associations of miRNA-27a and Leptin polymorphisms with the risk of recurrent spontaneous abortion (RSA). Material/Methods Between May 2013 and April 2015 at Shenzhen Longhua New District Central Hospital, we randomly recruited 138 RSA patients as the case group and another 142 normal pregnancy women as the control group. We used denaturing high-performance liquid chromatography (DHPLC) to determine the genotypes and allele frequencies of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A. Results The GG genotype and G allele frequencies of miRNA-27a rs895819 A/G were higher in the case group than in the control group, and the AA genotype and A allele frequencies of Leptin rs7799039 G/A were also higher in the case group than in the control group (all P<0.05). MiRNA-27a rs895819 A/G and Leptin rs7799039 G/A polymorphisms increased the risk of RSA (Exp (B)=2.732, 95% CI=1.625~4.596, P=0.000; Exp (B)=4.081, 95% CI=1.817~9.164, P=0.001). GG-AA or AG-AA carriers had a higher risk of RSA. The miRNA-27a expression of AA carriers of miRNA-27a rs895819 was lower than that of AG+GG carriers both in the case and control groups (all P=0.024). The plasma leptin concentration of GG carriers was lower than that of GA+AA carriers in the case group (P=0.026). Conclusions The polymorphisms of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A may contribute to an increased risk of RSA.
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Affiliation(s)
- Chun-Yan Wang
- Department of Obstetrics and Gynecology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China (mainland)
| | - Shu-Guang Wang
- Department of Obstetrics and Gynecology, Zaozhuang Maternity and Child Health Care Hospital, Zaozhuang, Shandong, China (mainland)
| | - Jia-Li Wang
- Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Li-Ying Zhou
- Department of Obstetrics and Gynecology, Shenzhen Longhua New District Central Hospital, Shenzhen, Guangdong, China (mainland)
| | - Hong-Jun Liu
- Department of Urology, Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Yi-Feng Wang
- Department of Obstetrics and Gynecology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China (mainland)
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Caparello C, Meijer LL, Garajova I, Falcone A, Le Large TY, Funel N, Kazemier G, Peters GJ, Vasile E, Giovannetti E. FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer. World J Gastroenterol 2016; 22:6987-7005. [PMID: 27610011 PMCID: PMC4988311 DOI: 10.3748/wjg.v22.i31.6987] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 06/09/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase III trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARC levels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microRNAs as predictive biomarkers.
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Baniak N, Senger JL, Ahmed S, Kanthan SC, Kanthan R. Gastric biomarkers: a global review. World J Surg Oncol 2016; 14:212. [PMID: 27514667 PMCID: PMC4982433 DOI: 10.1186/s12957-016-0969-3] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 08/02/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes. MAIN BODY This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability. CONCLUSION A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.
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Affiliation(s)
- Nick Baniak
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
| | - Jenna-Lynn Senger
- Department of Surgery, University of Alberta, 116 St & 85 Ave, Edmonton, T6G 2R3, T6G 2B7 AB Canada
| | - Shahid Ahmed
- Division of Medical Oncology, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
| | - S. C. Kanthan
- Department of General Surgery, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
| | - Rani Kanthan
- Department of General Surgery, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
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Biersack B. Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention. Noncoding RNA Res 2016; 1:12-34. [PMID: 30159408 PMCID: PMC6096431 DOI: 10.1016/j.ncrna.2016.07.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 07/20/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The epigenetic regulation of cancer cells by small non-coding RNA molecules, the microRNAs (miRNAs), has raised particular interest in the field of oncology. These miRNAs play crucial roles concerning pathogenic properties of cancer cells and the sensitivity of cancer cells towards anticancer drugs. Certain miRNAs are responsible for an enhanced activity of drugs, while others lead to the formation of tumor resistance. In addition, miRNAs regulate survival and proliferation of cancer cells, in particular of cancer stem-like cells (CSCs), that are especially drug-resistant and, thus, cause tumor relapse in many cases. Various small molecule compounds were discovered that target miRNAs that are known to modulate tumor aggressiveness and drug resistance. This review comprises the effects of naturally occurring small molecules (phenolic compounds and terpenoids) on miRNAs involved in cancer diseases.
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Key Words
- 1,25-D, 1,25-dihydroxyvitamin D3
- 18-AGA, 18α-glycyrrhetinic acid
- 3,6-DHF, 3,6-dihydroxyflavone
- AKBA, 3-acetyl-11-keto-β-boswellic acid
- Anticancer drugs
- CAPE, caffeic acid phenethyl ester
- CDODA-Me, methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate
- Dox, doxorubicin
- EGCG, (−)-epigallocatechin-3-O-gallate
- MicroRNA
- PEG, polyethylene glycol
- PPAP, polycyclic polyprenylated acylphloroglucinol
- Polyphenols
- RA, retinoic acid
- ROS, reactive oxygen species
- TQ, thymoquinone
- Terpenes
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Affiliation(s)
- Bernhard Biersack
- Organic Chemistry Laboratory, University of Bayreuth, Universitätsstraße 30, 95447 Bayreuth, Germany
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42
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Matboli M, El-Nakeep S, Hossam N, Habieb A, Azazy AEM, Ebrahim AE, Nagy Z, Abdel-Rahman O. Exploring the role of molecular biomarkers as a potential weapon against gastric cancer: A review of the literature. World J Gastroenterol 2016; 22:5896-5908. [PMID: 27468184 PMCID: PMC4948264 DOI: 10.3748/wjg.v22.i26.5896] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/25/2016] [Accepted: 06/13/2016] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging II-IV. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.
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43
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Wan QS, Zhang KH. Noninvasive detection of gastric cancer. Tumour Biol 2016; 37:11633-11643. [PMID: 27381515 DOI: 10.1007/s13277-016-5129-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC) is the fifth most common cancer and the third common cause of cancer death worldwide. Endoscopy is the most effective method for GC screening, but its application is limited by the invasion. Therefore, continuous efforts have been made to develop noninvasive methods for GC detection and promising results have been reported. Here, we review the advances in GC detection by protein and nucleic acid tumor markers, circulating tumor cells, and tumor-associated autoantibodies in peripheral blood. Some potential new noninvasive methods for GC detection are also reviewed, including exhaled breath analysis, blood spectroscopy analysis and molecular imaging.
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Affiliation(s)
- Qin-Si Wan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China
| | - Kun-He Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China.
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44
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Xie M, Dart DA, Owen S, Wen X, Ji J, Jiang W. Insights into roles of the miR-1, -133 and -206 family in gastric cancer (Review). Oncol Rep 2016; 36:1191-8. [PMID: 27349337 DOI: 10.3892/or.2016.4908] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 01/27/2016] [Indexed: 11/06/2022] Open
Abstract
Gastric cancer (GC) remains the third most common cause of cancer deaths worldwide and carries a high rate of metastatic risk contributing to the main cause of treatment failure. An accumulation of data has resulted in a better understanding of the molecular network of GC, however, gaps still exist between the unique bio-resources and clinical application. MicroRNAs are an important part of non-coding RNAs and behave as major regulators of tumour biology, alongside their well-known roles as intrinsic factors of gene expression in cellular processes, via their post-transcriptional regulation of components of signalling pathways in a coordinated manner. Deregulation of the miR-1, -133 and -206 family plays a key role in tumorigenesis, progression, invasion and metastasis. This review aims to provide a summary of recent findings on the miR-1, -133 and -206 family in GC and how this knowledge might be exploited for the development of future miRNA-based therapies for the treatment of GC.
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Affiliation(s)
- Meng Xie
- Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China
| | - Dafydd Alwyn Dart
- Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
| | - Sioned Owen
- Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
| | - Xianzi Wen
- Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China
| | - Jiafu Ji
- Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China
| | - Wenguo Jiang
- Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
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45
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Tsai MM, Wang CS, Tsai CY, Huang HW, Chi HC, Lin YH, Lu PH, Lin KH. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer. Int J Mol Sci 2016; 17:945. [PMID: 27322246 PMCID: PMC4926478 DOI: 10.3390/ijms17060945] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 06/01/2016] [Accepted: 06/07/2016] [Indexed: 12/11/2022] Open
Abstract
Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients' survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.
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Affiliation(s)
- Ming-Ming Tsai
- Department of Nursing, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan.
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
| | - Chia-Siu Wang
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
| | - Chung-Ying Tsai
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Hsiang-Wei Huang
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Hsiang-Cheng Chi
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Yang-Hsiang Lin
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Pei-Hsuan Lu
- Department of Dermatology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
| | - Kwang-Huei Lin
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
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Nakata W, Uemura M, Sato M, Fujita K, Jingushi K, Ueda Y, Kitae K, Tsujikawa K, Nonomura N. Expression of miR-27a-3p is an independent predictive factor for recurrence in clear cell renal cell carcinoma. Oncotarget 2016; 6:21645-54. [PMID: 26046464 PMCID: PMC4673293 DOI: 10.18632/oncotarget.4064] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2015] [Accepted: 05/15/2015] [Indexed: 01/16/2023] Open
Abstract
MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and function in tumor development and progression. We previously identified up-regulated miRNAs in clear cell renal cell carcinoma (ccRCC) compared to matched-pair normal kidney by microarray. Here, we identify miRNAs that are up-regulated in ccRCC and are also correlated with survival and/or recurrence. Twenty-four samples from ccRCC patients who underwent nephrectomies between 2011 and 2012 were divided into two groups: one of eleven patients who experienced recurrence (Group 1), and one of thirteen patients with no evidence of disease (Group 2) 2 years after surgery. Analyzing 22 miRNAs that were up-regulated in ccRCC in our previous study, we identify five miRNAs that were statistically up-regulated in Group 1 versus Group 2 by quantitative real-time PCR. We then evaluated these miRNAs in an independent cohort of 159 frozen ccRCC samples. High levels of miR-27a-3p (p < 0.01) correlated with a worse progression-free survival rate. Multivariate analysis revealed that miR-27a-3p was an independent predictive factor for recurrence. For functional analysis, miR-27a-3p controlled cell proliferation, migration and invasion in RCC cell lines. MiR-27a-3p could act as oncogenic miRNA and may be a candidate for targeted molecular therapy in ccRCC.
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Affiliation(s)
- Wataru Nakata
- The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Motohide Uemura
- The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Mototaka Sato
- The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazutoshi Fujita
- The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kentaro Jingushi
- Laboratory of Molecular and Cellular Physiology, Osaka University Graduate School of Pharmaceutical Sciences, Osaka, Japan
| | - Yuko Ueda
- Laboratory of Molecular and Cellular Physiology, Osaka University Graduate School of Pharmaceutical Sciences, Osaka, Japan
| | - Kaori Kitae
- Laboratory of Molecular and Cellular Physiology, Osaka University Graduate School of Pharmaceutical Sciences, Osaka, Japan
| | - Kazutake Tsujikawa
- Laboratory of Molecular and Cellular Physiology, Osaka University Graduate School of Pharmaceutical Sciences, Osaka, Japan
| | - Norio Nonomura
- The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
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47
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Wang S, Yuan L. Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine. Biosci Trends 2016; 10:171-80. [PMID: 27251446 DOI: 10.5582/bst.2016.01078] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer. The treatment of GC remains challenging as the outcomes achieved with surgery alone or adjuvant or neoadjuvant chemotherapy and radiotherapy are relatively poor. New treatment strategies are emerging and are being tested in solid tumors including GC. Over the past few years, the treatment of metastatic colorectal cancer (CRC) has made great advances, but strategies to manage GC have improved little. Multiple drug resistance is common in GC chemotherapy and targeted therapy; some patients appear to receive treatment that is suboptimal or even inefficacious. Unfortunately, there are few validated predictive biomarkers to guide the tailored treatment of GC. ToGA and AVAGAST are two phase III trials that tested the efficacy and safety of targeted agents in advanced gastric cancer (AGC), and results clearly indicated that patients need to be selected and that targeted agents are the best hope for better results. This review aims to provide an overview of potential predictive biomarkers for cytotoxic and targeted agents in GC.
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Affiliation(s)
- Shalong Wang
- Geriatric Surgery Department, Second Xiangya Hospital Affiliated with Central South University
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48
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Weiss M, Brandenburg LO, Burchardt M, Stope MB. MicroRNA-1 properties in cancer regulatory networks and tumor biology. Crit Rev Oncol Hematol 2016; 104:71-7. [PMID: 27286699 DOI: 10.1016/j.critrevonc.2016.05.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 04/18/2016] [Accepted: 05/25/2016] [Indexed: 02/07/2023] Open
Abstract
Short non-coding microRNAs have been identified to orchestrate crucial mechanisms in cancer progression and treatment resistance. MicroRNAs are involved in posttranscriptional modulation of gene expression and therefore represent promising targets for anticancer therapy. As mircoRNA-1 (miR-1) exerted to be predominantly downregulated in the majority of examined tumors, miR-1 is classified to be a tumor suppressor with high potential to diminish tumor development and therapy resistance. Here we review the complex functionality of miR-1 in tumor biology.
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Affiliation(s)
- Martin Weiss
- Department of Urology, University Medicine Greifswald, Greifswald, Germany
| | | | - Martin Burchardt
- Department of Urology, University Medicine Greifswald, Greifswald, Germany
| | - Matthias B Stope
- Department of Urology, University Medicine Greifswald, Greifswald, Germany.
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49
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Smid D, Kulda V, Srbecka K, Kubackova D, Dolezal J, Daum O, Kucera R, Topolcan O, Treska V, Skalicky T, Pesta M. Tissue microRNAs as predictive markers for gastric cancer patients undergoing palliative chemotherapy. Int J Oncol 2016; 48:2693-703. [PMID: 27081844 DOI: 10.3892/ijo.2016.3484] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 03/09/2016] [Indexed: 11/05/2022] Open
Abstract
MicroRNAs have the potential to become valuable predictive markers for gastric cancer. Samples of biopsy tissue, routinely taken from gastric cancer patients undergoing palliative chemotherapy, constitute suitable material for microRNA profiling with the aim of predicting the effect of chemotherapy. Our study group consisted of 54 patients, all of whom underwent palliative chemotherapy based on 5-fluorouracil (5-FU) or 5-FU in combination with platinum derivatives between 2000 and 2013. The expression of 29 selected microRNAs and genes BRCA1, ERCC1, RRM1 and TS, in gastric cancer tissue macrodissected from FFPE tissue samples, was measured by quantitative RT-PCR. The relationship between gene expression levels and time to progression (TTP) and overall survival (OS) was analysed. From the set of the 29 microRNAs of interest, we found high expression of miR-150, miR-342-3p, miR-181b, miR-221, miR-224 and low levels of miR-520h relate to shorter TTP. High levels of miR-150, miR-192, miR-224, miR-375 and miR-342-3p related to shorter OS. In routinely available FFPE tissue samples, we found 6 miRNAs with a relation to TTP, which may serve as predictors of the effectiveness of palliative treatment in gastric cancer patients. These miRNAs could also help in deciding whether to indicate palliative chemotherapy.
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Affiliation(s)
- David Smid
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30460, Czech Republic
| | - Vlastimil Kulda
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30166, Czech Republic
| | - Kristyna Srbecka
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30166, Czech Republic
| | - Dasa Kubackova
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30460, Czech Republic
| | - Jan Dolezal
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30460, Czech Republic
| | - Ondrej Daum
- Department of Pathology, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30599, Czech Republic
| | - Radek Kucera
- Department of Nuclear Medicine-Immunoanalytic Laboratory, University Hospital in Pilsen, Pilsen 30599, Czech Republic
| | - Ondrej Topolcan
- Department of Nuclear Medicine-Immunoanalytic Laboratory, University Hospital in Pilsen, Pilsen 30599, Czech Republic
| | - Vladislav Treska
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30460, Czech Republic
| | - Tomas Skalicky
- Department of Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 30460, Czech Republic
| | - Martin Pesta
- Department of Biology, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen 32600, Czech Republic
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Emerging Role of miRNAs in the Drug Resistance of Gastric Cancer. Int J Mol Sci 2016; 17:424. [PMID: 27011182 PMCID: PMC4813275 DOI: 10.3390/ijms17030424] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 03/11/2016] [Accepted: 03/16/2016] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer is the third leading cause of cancer mortality worldwide. Unfortunately, most gastric cancer cases are diagnosed in an advanced, non-curable stage and with a limited response to chemotherapy. Drug resistance is one of the most important causes of therapy failure in gastric cancer patients. Although the mechanisms of drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of microRNAs in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of malignancies, including gastric cancer. This review summarizes the current knowledge about the miRNAs’ characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant gastric cancer.
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