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Andrade R, Ribeiro IP, Carreira IM, Tralhão JG. The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma. Int J Mol Sci 2024; 25:6002. [PMID: 38892191 PMCID: PMC11172565 DOI: 10.3390/ijms25116002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/13/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA's early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA.
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Affiliation(s)
- Rita Andrade
- Surgery Department, Centro Hospitalar e Universitario de Coimbra EPE (CHUC), 3000-075 Coimbra, Portugal;
- Clinical Academic Center of Coimbra, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ilda Patrícia Ribeiro
- Clinical Academic Center of Coimbra, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Coimbra Institute for Clinical and Biomedical Research (CBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
| | - Isabel Marques Carreira
- Clinical Academic Center of Coimbra, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Coimbra Institute for Clinical and Biomedical Research (CBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
| | - José Guilherme Tralhão
- Surgery Department, Centro Hospitalar e Universitario de Coimbra EPE (CHUC), 3000-075 Coimbra, Portugal;
- Clinical Academic Center of Coimbra, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Coimbra Institute for Clinical and Biomedical Research (CBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
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Shobeiri P, Arabzadeh Bahri R, Khadembashiri MM, Khadembashiri MA, Maleki S, Eslami M, Khalili Dehkordi M, Behnoush AH, Rezaei N. Role of long non-coding RNAs in cholangiocarcinoma: A systematic review and meta-analysis. Cancer Rep (Hoboken) 2024; 7:e2029. [PMID: 38517409 PMCID: PMC10959185 DOI: 10.1002/cnr2.2029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 02/12/2024] [Accepted: 02/21/2024] [Indexed: 03/23/2024] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA), as a rare malignancy of the biliary tree, has a poor prognosis most of the time. CCA is highly epigenetically regulated and several long non-coding RNAs (lncRNA) have been investigated to have a diagnostic and prognostic role in CCA. The current study aimed to assess the studies finding relevant lncRNAs in CCA systematically. METHODS International databases, including PubMed, Cochrane Library, and Embase, were comprehensively searched in order to identify studies investigating any lncRNA in CCA. After screening by title/abstract and full-text, necessary data were extracted. Random-effect meta-analysis was performed for pooling the areas under the curve (AUCs), specificity, and sensitivity of lncRNAs for the diagnosis of CCA. RESULTS A total of 33 studies were chosen to be included in the final analysis, comprised of 2677 patients. Meta-analysis of AUCs for evaluation of CCA resulted in pooled AUC of 0.79 (95% CI: 0.75-0.82; I2 = 69.11, p < .01). Additionally, overall sensitivity of 0.80 (95% CI 0.75-0.84) and specificity of 0.77 (95% CI: 0.68-0.84) were observed. Measurement of lncRANs in the assessment of CCA also improved overall survival significantly (effect size 1.61, 95% CI: 1.39-1.82). A similar result was found for progression-free survival (effect size 1.57, 95% CI: 1.20-1.93). CONCLUSION Based on our findings, lncRNAs showed promising results as biomarkers in the diagnosis of CCA since they had acceptable sensitivity and specificity, in addition to the fact that improved survival in this poor prognosis cancer. Further studies might be needed to address this issue and find the best clinically useful lncRNA.
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Affiliation(s)
- Parnian Shobeiri
- School of medicineTehran University of Medical SciencesTehranIran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), TehranIran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical CenterTehran University of Medical SciencesTehranIran
| | - Razman Arabzadeh Bahri
- School of medicineTehran University of Medical SciencesTehranIran
- Urology Research CenterTehran University of Medical SciencesTehranIran
| | - Mohamad Mehdi Khadembashiri
- Neuromusculoskeletal Research CenterIran University of Medical SciencesTehranIran
- Student Scientific Research Center (SSRC)Tehran University of Medical SciencesTehranIran
| | - Mohamad Amin Khadembashiri
- Neuromusculoskeletal Research CenterIran University of Medical SciencesTehranIran
- Student Scientific Research Center (SSRC)Tehran University of Medical SciencesTehranIran
| | - Saba Maleki
- School of MedicineGuilan University of Medical SciencesRashtIran
| | - Mohammad Eslami
- Student Scientific Research Center (SSRC)Tehran University of Medical SciencesTehranIran
| | | | - Amir Hossein Behnoush
- School of medicineTehran University of Medical SciencesTehranIran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), TehranIran
| | - Nima Rezaei
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), TehranIran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical CenterTehran University of Medical SciencesTehranIran
- Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
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RPNs Levels Are Prognostic and Diagnostic Markers for Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:7270541. [PMID: 36072976 PMCID: PMC9444382 DOI: 10.1155/2022/7270541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/04/2022] [Accepted: 05/23/2022] [Indexed: 11/17/2022]
Abstract
The ribophorin family (RPN) is an essential regulatory subunit of the proteasome. By influencing the ubiquitin-proteasome system activity, ribophorins (RPNs) are responsible for almost all physiology and pathology processes of mammalian cells. Nevertheless, little is known about the role of RPNs in HCC. In this work, we first evaluated the transcriptional levels and the prognostic and diagnostic value of RPNs based on the public database. Firstly, we found all RPNs were surprisingly consistently upregulated in HCC tissues. Moreover, the RPNs' expression pattern is correlated with HCC tumor grade. The TCGA HCC platforms' data indicated that RPN2, RPN3, RPN6, RPN9, RPN10, RPN11, and RPN12 have robust diagnosis values. Then, survival analysis revealed that the high expression of RPN1, RPN2, RPN4, RPN5, RPN6, RPN9, and RPN11 was correlated with unfavourable HCC overall survival. Then, genetic alteration, immune infiltration feature, gene-genes network, and functional enrichment for RPNs indicated that RPNs have many potential biosynthesis activities expert for UPS functions. Moreover, western blot and qRT-PCR results confirmed these results. The silencing of RPN6 and RPN9 significantly reduced HCC cells' proliferation, migration, and invasion ability in vitro. An in vivo tumor model further validated the oncogene effect of RPN6 on HCC cell growth. Moreover, RPN6 and RPN9 could promote cell migratory and invasive potential by affecting the epithelial-mesenchymal transition (EMT) process. In summary, this study suggests that the RPN family has the potential to be potential biomarkers and targets for HCC.
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Wu Y, Hayat K, Hu Y, Yang J. Long Non-Coding RNAs as Molecular Biomarkers in Cholangiocarcinoma. Front Cell Dev Biol 2022; 10:890605. [PMID: 35573683 PMCID: PMC9093656 DOI: 10.3389/fcell.2022.890605] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/10/2022] [Indexed: 11/13/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a biliary system cancer that has the characteristics of strong invasiveness, poor prognosis, and few therapy choices. Furthermore, the absence of precise biomarkers for early identification and prognosis makes it hard to intervene in the early phase of initial diagnosis or recurring cholangiocarcinoma following surgery. Encouragingly, previous studies found that long non-coding RNA (lncRNA), a subgroup of RNA that is more than 200 nucleotides long, can affect cell proliferation, migration, apoptosis, and even drug resistance by altering numerous signaling pathways, thus reaching pro-cancer or anti-cancer outcomes. This review will take a retrospective view of the recent investigations on the work of lncRNAs in cholangiocarcinoma progression and the potential of lncRNAs serving as promising clinical biomarkers and therapeutic targets for CCA.
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Affiliation(s)
- Yanhua Wu
- Department of Gastroenterology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Khizar Hayat
- Department of Gastroenterology, International Education College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yufei Hu
- Department of Gastroenterology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jianfeng Yang
- Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
- *Correspondence: Jianfeng Yang,
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5
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Abedi Kichi Z, Soltani M, Rezaei M, Shirvani-Farsani Z, Rojhannezhad M. The Emerging role of EMT-related lncRNAs in therapy resistance and their application as biomarkers. Curr Med Chem 2022; 29:4574-4601. [PMID: 35352644 DOI: 10.2174/0929867329666220329203032] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/15/2022] [Accepted: 01/19/2022] [Indexed: 12/09/2022]
Abstract
Cancer is the world's second largest cause of death. The most common cancer treatments are surgery, radiation therapy, and chemotherapy. Drug resistance, epithelial-to-mesenchymal transition (EMT), and metastasis are all pressing issues in cancer therapy today. Increasing evidence showed that drug-resistant and EMT are co-related with each other. Indeed, drug-resistant cancer cells possess enhanced EMT and invasive ability. Recent researches have demonstrated lncRNAs (long noncoding RNAs) are noncoding transcripts, which play an important role in the regulation of EMT, metastasis, and drug resistance in different cancers. However, the relationships among lncRNAs, EMT, and drug resistance are still unclear. These effects could be exerted via several signaling pathways such as TGF-β, PI3K-AKT, and Wnt/β-catenin. Identifying the crucial regulatory roles of lncRNAs in these pathways and processes leads to the development of novel targeted therapies. We review the key aspects of lncRNAs associated with EMT and therapy resistance. We focus on the crosstalk between lncRNAs and molecular signaling pathways affecting EMT and drug resistance. Moreover, each of the mentioned lncRNAs could be used as a potential diagnostic, prognostic, and therapeutic biomarker for cancer. Although, there are still many challenges to investigate lncRNAs for clinical applications.
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Affiliation(s)
- Zahra Abedi Kichi
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University Munich, Germany
| | - Mona Soltani
- Department of Plant Production & Genetics, Faculty of Agriculture, Zanjan University, Zanjan, Iran
| | - Mina Rezaei
- Department of Cell and Molecular Biology, Faculty of life Sciences and Technology, Shahid Beheshti University, Tehran, IR Iran
| | - Zeinab Shirvani-Farsani
- Department of Cell and Molecular Biology, Faculty of life Sciences and Technology, Shahid Beheshti University, Tehran, IR Iran
| | - Mahbubeh Rojhannezhad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IR Iran
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6
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TÜNCEL Ö, KARA M, YAYLAK B, ERDOĞAN İ, AKGÜL B. Noncoding RNAs in apoptosis: identification and function. Turk J Biol 2021; 46:1-40. [PMID: 37533667 PMCID: PMC10393110 DOI: 10.3906/biy-2109-35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 02/08/2022] [Accepted: 11/14/2021] [Indexed: 08/04/2023] Open
Abstract
Apoptosis is a vital cellular process that is critical for the maintenance of homeostasis in health and disease. The derailment of apoptotic mechanisms has severe consequences such as abnormal development, cancer, and neurodegenerative diseases. Thus, there exist complex regulatory mechanisms in eukaryotes to preserve the balance between cell growth and cell death. Initially, protein-coding genes were prioritized in the search for such regulatory macromolecules involved in the regulation of apoptosis. However, recent genome annotations and transcriptomics studies have uncovered a plethora of regulatory noncoding RNAs that have the ability to modulate not only apoptosis but also many other biochemical processes in eukaryotes. In this review article, we will cover a brief summary of apoptosis and detection methods followed by an extensive discussion on microRNAs, circular RNAs, and long noncoding RNAs in apoptosis.
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Affiliation(s)
- Özge TÜNCEL
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - Merve KARA
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - Bilge YAYLAK
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - İpek ERDOĞAN
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - Bünyamin AKGÜL
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
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7
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Safarpour AR, Askari H, Ejtehadi F, Azarnezhad A, Raeis-Abdollahi E, Tajbakhsh A, Abazari MF, Tarkesh F, Shamsaeefar A, Niknam R, Sivandzadeh GR, Lankarani KB, Ejtehadi F. Cholangiocarcinoma and liver transplantation: What we know so far? World J Gastrointest Pathophysiol 2021; 12:84-105. [PMID: 34676129 PMCID: PMC8481789 DOI: 10.4291/wjgp.v12.i5.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/28/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.
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Affiliation(s)
- Ali Reza Safarpour
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Hassan Askari
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Farshid Ejtehadi
- The Princess Alexandra Hospital HNS Trust, Harlow, Essex CM20 1QX, United Kingdom
| | - Asaad Azarnezhad
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj 6617913446, Iran
| | - Ehsan Raeis-Abdollahi
- Department of Basic Medical Sciences, Qom Medical Branch, Islamic Azad University, Qom, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran 1417653761, Iran
| | - Firoozeh Tarkesh
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Alireza Shamsaeefar
- Shiraz Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran
| | - Ramin Niknam
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Gholam Reza Sivandzadeh
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | | | - Fardad Ejtehadi
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
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8
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Cigliano A, Chen X, Calvisi DF. Current challenges to underpinning the genetic basis for cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:511-526. [PMID: 33888034 PMCID: PMC8173760 DOI: 10.1080/17474124.2021.1915128] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 04/07/2021] [Indexed: 12/23/2022]
Abstract
AREAS COVERED This review provides an overview regarding the current scenario and knowledge of the CCA genomic landscape and the potentially actionable molecular aberrations in each CCA subtype. EXPERT OPINION The establishment and advances of high-throughput methodologies applied to genetic and epigenetic profiling are changing many cancer types' therapeutic landscape , including CCA.The large body of data generated must be interpreted appropriately and eventually implemented in clinical practice. The following advancements toward precision medicine in CCA management will require designing better clinical trials with improved methods to stratify biliary tumor patients.
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Affiliation(s)
- Antonio Cigliano
- Department of Medical, Surgery and Experimental Sciences, Division of Experimental Pathology and Oncology, University of Sassari, Italy
| | - Xin Chen
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California, USA
| | - Diego F. Calvisi
- Institute of Pathology, University of Regensburg, Regensburg, Germany
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9
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Ramli S, Sim MS, Guad RM, Gopinath SCB, Subramaniyan V, Fuloria S, Fuloria NK, Choy KW, Rana S, Wu YS. Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions. JOURNAL OF ONCOLOGY 2021; 2021:5519720. [PMID: 33936199 PMCID: PMC8055404 DOI: 10.1155/2021/5519720] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/15/2021] [Accepted: 03/26/2021] [Indexed: 02/08/2023]
Abstract
The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.
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Affiliation(s)
- Suaidah Ramli
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Maw Shin Sim
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Rhanye M. Guad
- Department of Biomedical Science and Therapeutics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Subash C. B Gopinath
- School of Bioprocess Engineering, Universiti Malaysia Perlis, Arau 02600, Perlis, Malaysia
- Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, Kangar 01000, Perlis, Malaysia
| | - Vetriselvan Subramaniyan
- Department of Pharmacology, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor 42610, Malaysia
| | - Shivkanya Fuloria
- Faculty of Pharmacy, AIMST University, Bedong, Kedah 08100, Malaysia
| | - Neeraj K. Fuloria
- Faculty of Pharmacy, AIMST University, Bedong, Kedah 08100, Malaysia
| | - Ker Woon Choy
- Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Shah Alam, Sungai Buloh 47000, Selangor, Malaysia
| | - Sohel Rana
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore-7400, Bangladesh
| | - Yuan Seng Wu
- Department of Biochemistry, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor 42610, Malaysia
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10
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Hosseini NF, Manoochehri H, Khoei SG, Sheykhhasan M. The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study. Curr Mol Med 2021; 21:96-110. [PMID: 32560605 DOI: 10.2174/1566524020666200619124543] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/30/2020] [Accepted: 05/04/2020] [Indexed: 02/08/2023]
Abstract
In various cancers, high-grade tumor and poor survival rate in patients with upregulated lncRNAs UCA1 have been confirmed. Urothelial carcinoma associated 1 (UCA1) is an oncogenic non-coding RNA with a length of more than 200 nucleotides. The UCA1 regulate critical biological processes that are involved in cancer progression, including cancer cell growth, invasion, migration, metastasis, and angiogenesis. So It should not surprise that UCA1 overexpresses in variety of cancers type, including pancreatic cancer, ovarian cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, endometrial cancer, cervical cancer, bladder cancer, adrenal cancer, hypopharyngeal cancer, oral cancer, gallbladder cancer, nasopharyngeal cancer, laryngeal cancer, osteosarcoma, esophageal squamous cell carcinoma, renal cell carcinoma, cholangiocarcinoma, leukemia, glioma, thyroid cancer, medulloblastoma, hepatocellular carcinoma and multiple myeloma. In this article, we review the biological function and regulatory mechanism of UCA1 in several cancers and also, we will discuss the potential of its as cancer biomarker and cancer treatment.
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Affiliation(s)
- Nashmin Fayazi Hosseini
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hamed Manoochehri
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | | | - Mohsen Sheykhhasan
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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11
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Merdrignac A, Papoutsoglou P, Coulouarn C. Long Noncoding RNAs in Cholangiocarcinoma. Hepatology 2021; 73:1213-1226. [PMID: 32865244 DOI: 10.1002/hep.31534] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/30/2020] [Accepted: 08/13/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Aude Merdrignac
- InsermUniv RennesNuMeCan (Nutrition Metabolisms and Cancer)UMR_S 1241CHU Rennes, F-35000RennesFrance
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12
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A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma. Aging (Albany NY) 2021; 13:2959-2981. [PMID: 33472169 PMCID: PMC7880389 DOI: 10.18632/aging.202446] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 11/23/2020] [Indexed: 12/21/2022]
Abstract
Cholangiocarcinoma (CCA) is a fatal disease with dismal survival rates. Long non-coding RNA (lncRNA) expression profiling as potential prognostic biomarkers play critical roles in tumor initiation, development, and poor prognosis. Identifying specific lncRNA to predict the prognosis of CCA patients in the early stages is very important for improving a patient’s survival. In the current study, we aimed to establish a novel risk-stratification lncRNA signature panel in CCA. The initial lncRNA discovery was identified in The Cancer Genome Atlas database (TCGA cohort). The Cox regression analysis was used to establish the lncRNA prognostic model and the receiver operating characteristic (ROC) curve analysis was performed to assess the specificity and sensitivity of the model. This was followed by independent validation of the lncRNA signature in the CCA patients from the First Affiliated Hospital of Wenzhou Medical University (WMU cohort). Furthermore, by using the Gene Ontology function and Kyoto Encyclopedia Gene and Genome pathway enrichment analysis, we explored the potential function of prognosis lncRNA. Finally, five lncRNA (HULC; AL359715.5; AC006504.8; AC090114.2; AP00943.4) were screened to establish the predictive model that significantly associated with poor overall survival(HR:4.879;95%CI,1.587-14.996;p=0.006). This five-lncRNA signature model showed excellent accuracy in the TCGA cohort (AUC=0.938), and also robustly predicted survival in the validation WMU cohort(AUC=0.816). Functional enrichment analysis suggested prognostic lncRNA was primarily associated with CCA-related biological processes. Our data established a novel lncRNA signature model for CCA risk-stratification and robust identification of CCA patients with poor molecular genotypes. Moreover, it revealed new molecular mechanisms of CCA.
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Rodrigues PM, Olaizola P, Paiva NA, Olaizola I, Agirre-Lizaso A, Landa A, Bujanda L, Perugorria MJ, Banales JM. Pathogenesis of Cholangiocarcinoma. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2020; 16:433-463. [PMID: 33264573 DOI: 10.1146/annurev-pathol-030220-020455] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cholangiocarcinoma (CCA) encompasses a group of malignancies that can arise at any point in the biliary tree. Although considered a rare cancer, the incidence of CCA is increasing globally. The silent and asymptomatic nature of these tumors, particularly in their early stages, in combination with their high aggressiveness, intra- and intertumor heterogeneity, and chemoresistance, significantly compromises the efficacy of current therapeutic options, contributing to a dismal prognosis. During the last few years, increasing efforts have been made to unveil the etiologies and pathogenesis of these tumors and to develop more effective therapies. In this review, we summarize current findings in the field of CCA, mainly focusing on the mechanisms of pathogenesis, cells of origin, genomic and epigenetic abnormalities, molecular alterations, chemoresistance, and therapies.
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Affiliation(s)
- Pedro M Rodrigues
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; , .,National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Paula Olaizola
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; ,
| | - Nuno A Paiva
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; ,
| | - Irene Olaizola
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; ,
| | - Alona Agirre-Lizaso
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; ,
| | - Ana Landa
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; ,
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; , .,National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; , .,National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain; , .,National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain.,Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
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14
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Zhang J, Wang L, Jiang J, Qiao Z. The lncRNA SNHG15/miR-18a-5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway. J Cell Biochem 2020; 121:4699-4710. [PMID: 33135285 DOI: 10.1002/jcb.29474] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 10/10/2019] [Indexed: 12/13/2022]
Abstract
Here, we report the expression pattern, function and regulatory mechanism of SNHG15 together with miR-18a-5p micro RNA in ovarian cancer (OC) for the first time. We recruited 20 patients and took normal ovarian tissues and ovarian tumor tissues from them. We used cell culture, transfection, in vivo tumor xenograft assay, and multiple types of detection assays to investigate the expression and regulation of long noncoding RNA (lncRNA) SNHG15/miR-18a-5p in ovarian tissues and cells. Results: We found that the messenger RNA expression level of SNHG15 was significantly higher and miR-18 was decreased in ovarian cancer tissues and in OC cells. Functional experiments showed that SNHG15 overexpression potentiated the migration and invasion of OC cells, while SNHG15 inhibition reduced the tumor proliferation, which was restored via overexpression of miR-18a. SNHG15 was found to directly target and suppress the expression of miR-18a. Our results illustrate the possible molecular mechanism of lncRNA SNHG15/miR-18a-5p functions in cell proliferation in OC. SNHG15/miR-18a promoted the progression of OC cells via the protein kinase B/mammalian target of rapamycin signaling pathway.
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Affiliation(s)
- Jingru Zhang
- The Fourth Department of Gynaecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shengyang, Liaoning, China
| | - Ling Wang
- The Fourth Department of Gynaecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shengyang, Liaoning, China
| | - Jing Jiang
- The Fourth Department of Gynaecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shengyang, Liaoning, China
| | - Zhiwei Qiao
- The Fourth Department of Gynaecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shengyang, Liaoning, China
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15
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Vishwakarma S, Pandey R, Singh R, Gothalwal R, Kumar A. Expression of H19 long non-coding RNA is down-regulated in oral squamous cell carcinoma. J Biosci 2020. [DOI: 10.1007/s12038-020-00118-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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16
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Yang Y, Deng X, Li Q, Wang F, Miao L, Jiang Q. Emerging roles of long noncoding RNAs in cholangiocarcinoma: Advances and challenges. Cancer Commun (Lond) 2020; 40:655-680. [PMID: 33142045 PMCID: PMC7743012 DOI: 10.1002/cac2.12109] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/10/2020] [Accepted: 10/21/2020] [Indexed: 12/19/2022] Open
Abstract
Cholangiocarcinoma (CCA), a cancer with a relatively low incidence rate, is usually associated with poor prognosis. Current modalities for the diagnosis and treatment of CCA patients are still far from satisfactory. In recent years, numerous long noncoding RNAs (lncRNAs) have been identified as crucial players in the development of various cancers, including CCA. Abnormally expressed lncRNAs in CCA, regulated by some upstream molecules, significantly influence the biological behavior of tumor cells and are involved in tumor development through various mechanisms, including interactions with functional proteins, participation in competing for endogenous RNA (ceRNA) regulatory networks, activation of cancer‐related signaling pathways and epigenetic modification of gene expression. Furthermore, several lncRNAs are closely associated with the clinicopathological features of CCA patients, and are promising biomarkers for diagnosing and prognostication of CCA. Some of these lncRNAs play an important role in chemotherapy drug resistance. In addition, lncRNAs have also been shown to be involved in the inflammation microenvironment of CCA and malignant outcome of CCA risk factors, such as cholestatic liver diseases. In view of the difficulty of diagnosing CCA, more attention should be paid to detectable lncRNAs in the serum or bile. This review summarizes the recent knowledge on lncRNAs in CCA and provides a new outlook on the molecular mechanisms of CCA development from the perspective of lncRNAs. Moreover, we also discussed the limitations of the current studies and differential expression of lncRNAs in different types of CCA.
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Affiliation(s)
- Yang Yang
- Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.,Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China
| | - Xueting Deng
- Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.,Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China
| | - Quanpeng Li
- Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.,Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China
| | - Fei Wang
- Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.,Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China
| | - Lin Miao
- Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.,Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China
| | - Qi Jiang
- Department of Gastroenterology, Dongtai People's Hospital, Yancheng, Jiangsu, 224000, P. R. China
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17
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Burenina OY, Lazarevich NL, Kustova IF, Shavochkina DA, Moroz EA, Kudashkin NE, Patyutko YI, Metelin AV, Kim EF, Skvortsov DA, Zatsepin TS, Rubtsova MP, Dontsova OA. Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors. J Cancer Res Clin Oncol 2020; 147:49-59. [PMID: 32918630 DOI: 10.1007/s00432-020-03378-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE Liver cancers are among the deadliest malignancies due to a limited efficacy of early diagnostics, the lack of appropriate biomarkers and insufficient discrimination of different types of tumors by classic and molecular methods. In this study, we searched for novel long non-coding RNA (lncRNA) as well as validated several known candidates suitable as probable biomarkers for primary liver tumors of various etiology. METHODS We described a novel lncRNA HELIS (aka "HEalthy LIver Specific") and estimated its expression by RT-qPCR in 82 paired tissue samples from patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), combined HCC-CCA, pediatric hepatoblastoma (HBL) and non-malignant hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH). Additionally, we examined expression of cancer-associated lncRNAs HULC, MALAT1, UCA1, CYTOR, LINC01093 and H19, which were previously studied mainly in HCC. RESULTS We demonstrated that down-regulation of HELIS strongly correlates with carcinogenesis; whereas in tumors with non-hepatocyte origin (HBL, CCA) or in a number of poorly differentiated HCC, this lncRNA is not expressed. We showed that recently discovered LINC01093 is dramatically down-regulated in all malignant liver cancers; while in benign tumors LINC01093 expression is just twice decreased in comparison to adjacent samples. CONCLUSION Our study revealed that among all measured biomarkers only down-regulated HELIS and LINC01093, up-regulated CYTOR and dysregulated HULC are perspective for differential diagnostics of liver cancers; whereas others demonstrated discordant results and cannot be considered as potential universal biomarkers for this purpose.
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Affiliation(s)
- Olga Y Burenina
- Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia, 143026.
| | - Natalia L Lazarevich
- Institute of Carcinogenesis, FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478
- Biology Department, Lomonosov Moscow State University, Moscow, Russia, 119234
| | - Inna F Kustova
- Institute of Carcinogenesis, FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478
| | - Daria A Shavochkina
- Institute of Carcinogenesis, FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478
| | - Ekaterina A Moroz
- Institute of Clinical Oncology, FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478
| | - Nikolay E Kudashkin
- Institute of Clinical Oncology, FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478
| | - Yuriy I Patyutko
- Institute of Clinical Oncology, FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow, Russia, 115478
| | - Alexey V Metelin
- Petrovsky National Research Centre of Surgery, Moscow, Russia, 119991
| | - Eduard F Kim
- Petrovsky National Research Centre of Surgery, Moscow, Russia, 119991
| | - Dmitry A Skvortsov
- Lomonosov Moscow State University, Chemistry Department and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia, 119992
- Faculty of Biology and Biotechnologies, Higher School of Economics, Moscow, Russia, 101000
| | - Timofei S Zatsepin
- Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia, 143026
- Lomonosov Moscow State University, Chemistry Department and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia, 119992
| | - Maria P Rubtsova
- Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia, 143026
- Lomonosov Moscow State University, Chemistry Department and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia, 119992
| | - Olga A Dontsova
- Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, Russia, 143026
- Lomonosov Moscow State University, Chemistry Department and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia, 119992
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18
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Ma Z, Cai Y, Zhang L, Tian C, Lyu L. LINC00319 Promotes Cervical Cancer Progression Via Targeting miR-147a/IGF1R Pathway. Cancer Biother Radiopharm 2020:cbr.2020.3722. [PMID: 32644822 DOI: 10.1089/cbr.2020.3722] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: Cervical cancer is identified as the fourth most common female malignancy worldwide. Recently, Linc00319 was reported to play an important role in the development and progression of cervical cancer. However, little is known about the molecular mechanism and clinical significance of Linc00319 in the carcinogenesis of cervical cancer. This study aims to reveal the biological function and molecular mechanisms of Linc00319 in cell proliferation, invasion, and migration of cervical cancer. Materials and Methods: In the current study, gene expression levels of Linc00319, miR-147a, and IFG1R were detected by quantitative real-time PCR in clinical tissue samples and cervical cancer cell lines. Protein levels were also determined by western blot assay in cervical cancer cells. CCK-8, transwell, and wound healing assays were used to test the proliferation, invasion, and migration of cervical cancer cell lines in vitro. Target genes were predicted through bioinformatics methods and then verified by gene engineering technology. Results: The authors' results showed that Linc00319 was upregulated in cervical cancer tissues and cell lines, while Linc00319silencing could inhibit cervical cancer cell proliferation, invasion, and migration. Further investigations showed that Linc00319 interacted with miR-147a and inhibited its expression, unregulated IGF1R to induce progression of cervical cancer. Conclusions: Their research indicated that Linc00319 might play an oncogenic role in cervical cancer and regulate the progression of cervical tumor growth by inhibiting the expression of miR-147a and activating IGF1R-related pathway. The findings suggest a novel molecular biomarker and therapeutic target for cervical tumor and may provide a novel therapeutic strategy for preventing the metastasis of cervical cancer.
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Affiliation(s)
- Zhe Ma
- Department of Obstetrics and Gynecology, Affiliated Hospital of Beihua University, Jilin City, China
| | - Yufei Cai
- Department of Obstetrics and Gynecology, Affiliated Hospital of Beihua University, Jilin City, China
| | - Limei Zhang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Beihua University, Jilin City, China
| | - Chenchen Tian
- Department of Obstetrics and Gynecology, Affiliated Hospital of Beihua University, Jilin City, China
| | - Lin Lyu
- Department of Gynecology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City, China
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19
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Zhu B, Zhang S, Meng N, Zhang H, Yuan S, Zhang J. Long non-coding RNA RNCR3 promotes glioma progression involving the Akt/GSK-3β pathway. Oncol Lett 2019; 18:6315-6322. [PMID: 31788110 PMCID: PMC6865823 DOI: 10.3892/ol.2019.11002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 05/30/2019] [Indexed: 01/03/2023] Open
Abstract
Increasing evidence has confirmed that long non-coding RNAs (lncRNAs) serve critical roles in the development of a large number of human malignancies, including glioma. Several previously published studies have reported that the lncRNA retinal non-coding RNA3 (RNCR3; also termed LINC00599) exerts important roles in certain human malignancies; however, the precise biological role and underlying molecular mechanisms of RNCR3 in the development of glioma are yet to be fully elucidated. In the present study, it was revealed that the expression of RNCR3 was increased in glioma tissues compared with in corresponding adjacent normal tissues. Furthermore, increased levels of RNCR3 expression were associated with tumor progression and poor survival rates of patients with glioma. In addition, the U87 and U251 cell lines were selected to investigate the biological function and potential mechanisms of RNCR3 in glioma, and it was observed that RNCR3 knockdown led to an impairment of the proliferative and invasive abilities of cells; furthermore, G1 phase arrest was induced in glioma cells in vitro. Finally, the results of western blot analyses revealed that knockdown of RNCR3 led to a decrease in the expression levels of phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β), without any clear effect on the expression levels of total Akt and GSK-3β. Collectively, these results suggested that RNCR3 is able to regulate cell proliferation, the cell cycle and cell invasion in glioma, potentially via the Akt/GSK-3β signaling pathway.
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Affiliation(s)
- Bing Zhu
- Department of Neurosurgery, Sunshine Union Hospital of Shandong Province, Weifang, Shandong 216000, P.R. China
| | - Shenyan Zhang
- Department of Neurosurgery, Sunshine Union Hospital of Shandong Province, Weifang, Shandong 216000, P.R. China
| | - Ning Meng
- Department of Neurosurgery, Sunshine Union Hospital of Shandong Province, Weifang, Shandong 216000, P.R. China
| | - He Zhang
- Department of Neurosurgery, Sunshine Union Hospital of Shandong Province, Weifang, Shandong 216000, P.R. China
| | - Shaoji Yuan
- Department of Neurosurgery, Sunshine Union Hospital of Shandong Province, Weifang, Shandong 216000, P.R. China
| | - Jin Zhang
- Department of Neurosurgery, Sunshine Union Hospital of Shandong Province, Weifang, Shandong 216000, P.R. China
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20
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Downregulation of lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease through the inhibition of the PI3K/Akt signaling pathway. Int Immunopharmacol 2019; 75:105734. [PMID: 31301558 DOI: 10.1016/j.intimp.2019.105734] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 06/21/2019] [Accepted: 06/29/2019] [Indexed: 01/05/2023]
Abstract
This study is conducted to investigate the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in the protection of dopaminergic neurons in Parkinson's disease (PD) through regulating the PI3K/Akt signaling pathway. PD rat model was induced by injection of 6-hydroxydopamine (6-OHDA) to damage the substantia nigra striatum. The successfully modeled PD rats were introduced with siRNA-negative control (NC) or UCA1-siRNA. The expression of UCA1 in neurobehavioral change, neuroinflammatory response and oxidative stress of PD rats were explored. The effect of UCA1 on the PI3K/Akt signaling pathway and downstream proteins IκBα and ERK was also investigated. The rats with PD exhibited aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress. Down-regulation of UCA1 up-regulated the expression of TH positive cells and DA content, reduced the apoptosis of substantia nigra neurons, the apoptosis of substantia nigra neurons and oxidative stress and improved the neuroinflammatory response in PD rats. Down-regulation of UCA1 inhibited the activation of the PI3K/AKT signaling pathway in substantia nigra of PD rats. Our study suggests that the downregulated lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in PD rats through the inhibition of the PI3K/Akt signaling pathway.
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21
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UCA1 long non-coding RNA: An update on its roles in malignant behavior of cancers. Biomed Pharmacother 2019; 120:109459. [PMID: 31585301 DOI: 10.1016/j.biopha.2019.109459] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/06/2019] [Accepted: 09/12/2019] [Indexed: 12/24/2022] Open
Abstract
The lncRNA urothelial carcinoma-associated 1 (UCA1) is a 1.4 kb long transcript which has been firstly recognized in human bladder cancer cell line. Subsequent studies revealed its over-expression in a wide array of human cancer cell lines and patients' samples. In addition to conferring malignant phenotype to cells, it enhances resistance to conventional anti-cancer drugs. Moreover, transcript levels of this lncRNA have been regarded as diagnostic markers in several cancer types including gastric, bladder and liver cancers. The underlying mechanism of its participation in carcinogenesis has been identified in some cancer types. Sponging tumor suppressor miRNAs, interacting with cancer-promoting signaling pathways and enhancing cell cycle progression are among these mechanisms. Although few studies have shown anti-carcinogenic properties for this lncRNA, the bulk of evidence supports its oncogenic roles. In the current study, we have reviewed the current literature on the role of UCA1 in the carcinogenic process based on the results of in vitro studies, investigations in animal models and assessment of UCA1 expression in clinical samples.
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22
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Angenard G, Merdrignac A, Louis C, Edeline J, Coulouarn C. Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma. Dig Liver Dis 2019; 51:1337-1343. [PMID: 31040073 DOI: 10.1016/j.dld.2019.03.019] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/05/2019] [Accepted: 03/22/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide associated with an increased incidence, limited therapeutic options and absence of reliable prognostic biomarkers. Long non-coding RNAs (lncRNA) emerge as relevant biomarkers in cancer being associated with tumor progression. However, lncRNA have been poorly investigated in iCCA. AIM To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent. METHODS Gene expression profiling and Q-RT-PCR were performed from a cohort of 39 clinically well-annotated iCCA. Univariate Cox proportional hazards model with Wald Statistic was used to identify lncRNA significantly associated with overall (OS) and/or disease-free (DFS) survival. RESULTS A signature made of 9 lncRNA was identified to be significantly (P < 0.05) associated with OS and DFS, including 4 lncRNA (lnc-CDK9-1, XLOC_l2_009441, CDKN2B-AS1, HOXC13-AS) highly expressed in poor prognosis iCCA and 5 lncRNA (lnc-CCHCR1-1, lnc-AF131215.3.1, lnc-CBLB-5, COL18A1-AS2, lnc-RELL2-1) highly expressed in better prognosis iCCA. We further validated CDKN2B-AS1 (ANRIL) as a poor prognosis biomarker, not only in iCCA, but also in hepatocellular carcinoma, kidney renal clear cell carcinoma and uterine corpus endometrial carcinoma. CONCLUSIONS We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers.
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Affiliation(s)
- Gaëlle Angenard
- Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France
| | - Aude Merdrignac
- Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France
| | - Corentin Louis
- Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France
| | - Julien Edeline
- Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France
| | - Cédric Coulouarn
- Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France.
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23
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Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma. Cell Death Dis 2019; 10:585. [PMID: 31383847 PMCID: PMC6683119 DOI: 10.1038/s41419-019-1810-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Revised: 06/28/2019] [Accepted: 07/08/2019] [Indexed: 12/12/2022]
Abstract
Recently, long noncoding RNAs (lncRNAs) have been shown to play significant regulatory roles in human tumorigenesis. However, the biological function of lncRNAs in cholangiocarcinoma (CCA) remains largely unknown. In this study, DANCR was shown to be significantly upregulated in CCA. DANCR regulated the proliferation and migration of CCA cells in vitro. Moreover, downregulation of DANCR suppressed CCA cells proliferation in vivo. RNA-seq revealed that DANCR knockdown preferentially affected genes linked with cell proliferation and cell differentiation. Furthermore, mechanistic investigation validated that DANCR could bind EZH2 and modulate the histone methylation of promoter of FBP1, thereby regulating CCA cells growth and migration. Taken together, these results demonstrated the significant roles of DANCR in CCA and may provide a theoretical basis for clinical diagnosis and treatment of CCA.
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24
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Li O, Yi W, Yang P, Guo C, Peng C. Long non-coding RNA UCA1 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells through targeting microRNA-122. Exp Ther Med 2019; 18:25-32. [PMID: 31258634 DOI: 10.3892/etm.2019.7564] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 08/02/2018] [Indexed: 01/08/2023] Open
Abstract
Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) has a role in various common types of human malignancy, including cholangiocarcinoma; however, the expression and function of UCA1 in intrahepatic cholangiocarcinoma (ICC) has remained elusive. In the present study, it was observed that UCA1 expression was significantly upregulated in ICC tissues and cell lines compared with that in the adjacent non-tumour tissues and a human intrahepatic biliary epithelial cell line, respectively. The increased expression of UCA1 was significantly associated with lymph node metastasis and clinical T-stage in ICC. Furthermore, the ICC patients with high expression of UCA1 had a shorter survival time when compared with that of patients with low UCA1 expression. Knockdown of UCA1 caused a significant decrease in ICC cell proliferation and invasion, while ectopic overexpression of UCA1 significantly promoted the proliferation and invasion of ICC cells. Furthermore, it was revealed that UCA1 directly binds to microRNA (miR)-122 to negatively regulate its expression in ICC cells. In addition, miR-122 mimics abrogated the promoting effects of UCA1 on ICC cell proliferation and invasion. In addition, an inverse correlation between miR-122 and UCA1 expression in ICC tissues was observed. In conclusion, the present study demonstrates that the lncRNA UCA1 promotes ICC cell proliferation and invasion at least in part by targeting miR-122, suggesting that the UCA1/miR-122 interaction may become a potential therapeutic target for the treatment of ICC.
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Affiliation(s)
- Ou Li
- Department of Hepatobiliary Surgery, Hunan Province People's Hospital, Changsha, Hunan 410005, P.R. China
| | - Weimin Yi
- Department of Hepatobiliary Surgery, Hunan Province People's Hospital, Changsha, Hunan 410005, P.R. China
| | - Pingzhou Yang
- Department of Hepatobiliary Surgery, Hunan Province People's Hospital, Changsha, Hunan 410005, P.R. China
| | - Chao Guo
- Department of Hepatobiliary Surgery, Hunan Province People's Hospital, Changsha, Hunan 410005, P.R. China
| | - Chuang Peng
- Department of Hepatobiliary Surgery, Hunan Province People's Hospital, Changsha, Hunan 410005, P.R. China
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Long noncoding RNA UCA1 as a novel biomarker of lymph node metastasis and prognosis in human cancer: a meta-analysis. Biosci Rep 2019; 39:BSR20180995. [PMID: 30918102 PMCID: PMC6487270 DOI: 10.1042/bsr20180995] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 01/13/2019] [Accepted: 03/18/2019] [Indexed: 01/27/2023] Open
Abstract
Background: Urothelial carcinoma associated 1 (UCA1), a novel long noncoding RNA (lncRNA) which is first discovered in 2006 in human bladder cancer and has become a hot spot in recent years. UCA1 has been demonstrated correlated with clinical outcomes in various cancers. However, the results from each study are insufficient and not completely consistent. Therefore, we perform a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis of cancer. Methods: Relevant English literatures were searched in PubMed, Cochrane Library, Web of science, Embase databases and Chinese literatures were searched in Chinese National Knowledge Infrastructure Wanfang from inception up to 17 April 2018. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) using random/fixed-effect were used to identify the relationship between UCA1 and lymph node metastasis (LNM) or overall survival (OS) of cancer patients. Subgroup analysis and sensitivity analysis were performed. The current meta-analysis was performed using Review Manager 5.3 and Stata 12.0 software. Results: A total of 3411 patients from 38 studies were finally included. Patients who with high UCA1 expression suffered from an increased risk of LNM (OR = 2.50; 95% CI: 1.93–3.25). UCA1 was also significantly associated with OS (HR = 2.05; 95% CI: 1.77–2.38). Subgroup analyses across several different variables also showed the similar results in LNM and OS of cancer patients. Conclusion: High expression of UCA1 was linked with poor clinical outcome. UCA1 can serve as a potential molecular marker for metastasis and prognosis in different types of cancers.
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Hu X, Tan Z, Yang Y, Yang P. Long non‐coding RNA MIR22HG inhibits cell proliferation and migration in cholangiocarcinoma by negatively regulating the Wnt/β‐catenin signaling pathway. J Gene Med 2019; 21:e3085. [PMID: 30856284 DOI: 10.1002/jgm.3085] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 03/05/2019] [Accepted: 03/06/2019] [Indexed: 12/11/2022] Open
Affiliation(s)
- Xiahong Hu
- Department of Hepatobiliary SurgeryHunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha Hunan China
| | - Zhaoxia Tan
- Department of Hepatobiliary SurgeryHunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha Hunan China
| | - Yijiang Yang
- Department of Hepatobiliary SurgeryHunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha Hunan China
| | - Pinghui Yang
- Department of Hepatobiliary SurgeryHunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha Hunan China
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Li J, Huang L, Li Z, Zhong X, Tai S, Jiang X, Cui Y. Functions and roles of long noncoding RNA in cholangiocarcinoma. J Cell Physiol 2019; 234:17113-17126. [PMID: 30888066 DOI: 10.1002/jcp.28470] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 02/20/2019] [Indexed: 02/06/2023]
Abstract
Cholangiocarcinoma (CCA) is one of the most fatal cancers in humans, with a gradually increasing incidence worldwide. The efficient diagnostic and therapeutic measures for CCA to reduce mortality are urgently needed. Long noncoding RNAs (lncRNAs) may provide the potential diagnostic and therapeutic option for suppressing the CCA development. LncRNAs are a type of non-protein-coding RNAs, which are larger than 200 nucleotides in length. Increasing evidence reveals that lncRNAs exhibit critical roles in the carcinogenesis and development of CCA. Deregulation of lncRNAs impacts the proliferation, migration, invasion, and antiapoptosis of CCA cells by multiple sophisticated mechanisms. Consequently, lncRNAs likely represent promising biomarkers or intervention targets of CCA. In this review, we summarize current studies regarding the biological functions and regulatory mechanisms of diverse lncRNAs in CCA.
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Affiliation(s)
- Jinglin Li
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Lining Huang
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Zhenglong Li
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xiangyu Zhong
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Sheng Tai
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xingming Jiang
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yunfu Cui
- Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Zhang J, Zhang C. Silence of long non-coding RNA UCA1 inhibits hemangioma cells growth, migration and invasion by up-regulation of miR-200c. Life Sci 2019; 226:33-46. [PMID: 30898646 DOI: 10.1016/j.lfs.2019.03.038] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 03/14/2019] [Accepted: 03/16/2019] [Indexed: 11/26/2022]
Abstract
BACKGROUND Human urothelial carcinoma associated 1 (UCA1) has been recognized as an oncogenic lncRNA in various cancers, except infantile hemangioma (IH). This study attempts to explore the functional role of lncRNA UCA1 in IH. METHODS qRT-PCR was carried out to detect the expression of lncRNA UCA1 in human IH tissues. Two hemangioma cell lines (EOMA and HemECs) were transfected with shRNAs specific for lncRNA UCA1, or a plasmid for expression lncRNA UCA1. The expression of miR-200c in cell was suppressed or overexpressed by miRNA-mediated transfection. CCK-8 assay, flow cytometry, Transwell assay, and Western blot were performed to detect cell survival, migration and invasion. RESULTS LncRNA UCA1 was up-regulated in proliferating-phase hemangioma samples, as compared to involuting-phase. Silence of lncRNA UCA1 significantly reduced EOMA cells viability, migration and invasion, and induced apoptosis. These observations were coupled with the down-regulations of CyclinD1, CDK6 and CDK4, the cleavage of caspase-3 and caspase-9, as well as the decreased expression levels of MMP-9 and Vimentin. miR-200c was highly expressed in lncRNA UCA1 silenced-cells. Besides, the anti-tumor effects of lncRNA UCA1 silence towards EOMA cells were reversed by miR-200c suppression. Same effects of lncRNA UCA1 and miR-200c on HemECs cells were observed. Furthermore, silence of lncRNA UCA1 repressed mTOR, AMPK and Wnt/β-catenin signaling via a miR-200c-dependent fashion. CONCLUSION This study evidences that silence of lncRNA UCA1 inhibits hemangioma cells growth, migration and invasion possibly via its regulation on miR-200c expression and the activation of mTOR, AMPK and Wnt/β-catenin signaling pathways.
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Affiliation(s)
- Jing Zhang
- Department of Pediatric Surgery, Weifang People's Hospital, Weifang 261000, China
| | - Chuanguang Zhang
- Department of Pediatric Surgery, Weifang People's Hospital, Weifang 261000, China.
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Akirin2 is modulated by miR-490-3p and facilitates angiogenesis in cholangiocarcinoma through the IL-6/STAT3/VEGFA signaling pathway. Cell Death Dis 2019; 10:262. [PMID: 30886152 PMCID: PMC6423123 DOI: 10.1038/s41419-019-1506-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 02/15/2019] [Accepted: 03/04/2019] [Indexed: 02/08/2023]
Abstract
Akirin2 is a key regulator of embryonic development and the innate immunity response. However, this regulator’s role in tumorigenesis especially in cholangiocarcinoma (CCA) development has not been thoroughly elucidated to date. In the current work, we used RT-qPCR, western blot analysis, and immunohistochemistry (IHC) to explore the expression level of Akirin2, and the relationship between Akirin2 levels and clinicopathological characteristics was evaluated. The biological functions of Akirin2 were examined in vitro and in vivo by using a lentiviral vector system. Luciferase reporter assays were applied to detect the direct binding relationship between the 3′-UTR of Akirin2 mRNA and miR-490-3p. The results showed that Akirin2 was overexpressed in CCA and this upregulation was associated with a shorter overall survival. Silencing or overexpressing Akirin2 by lentiviral approaches significantly influenced CCA cell proliferation, migration, invasion, and angiogenesis. An in vivo tumor model further validated the oncogenic effect of Akirin2 on CCA cell growth, metastasis, and angiogenesis. Mechanistic studies demonstrated that Akirin2 induced angiogenesis by increasing the expression of VEGFA by activating the IL-6/STAT3 signaling pathway. Akirin2 promoted cell migratory and invasive potential by affecting the epithelial–mesenchymal transition (EMT) process. In addition, Akirin2 expression was negatively controlled by miR-490-3p in CCA cells, and miR-490-3p attenuated cell migration and angiogenesis in CCA cells by silencing Akirin2. Taken together, the data indicated that Akirin2 could be regulated by miR-490-3p at the posttranscriptional level and facilitate CCA cell progression via the IL-6/STAT3/VEGFA signaling pathway. The present study may expedite the development of novel therapeutic strategies for CCA.
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Dai K, Quan J, Yan F, Jin X, Pan X, Song X, Zhang S, Ren Q, Liu J, Liu X. lncRNAs as potential molecular biomarkers in the clinicopathology and prognosis of cholangiocarcinoma: a systematic review and meta-analysis. Onco Targets Ther 2019; 12:1905-1915. [PMID: 30881042 PMCID: PMC6415731 DOI: 10.2147/ott.s188134] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Cholangiocarcinoma (CCA) is the second most common fatal primary hepatobiliary malignant carcinoma, characterized by early invasion and extremely poor outcomes. It is therefore necessary to identify a novel biomarker to better diagnose CAA and predict its prognosis. Recently, emerging evidence has revealed that some lncRNAs play an important role in the tumorigenesis and progression of CAA. In order to support this search for novel diagnostic and prognostic biomarkers for CAA, we conducted a meta-analysis to analyze the published association between lncRNA expression and its clinical value in CAA. Methods Eligible studies were pooled and analyzed according to our inclusion and exclusion criteria after a comprehensive literature search. Stata 14.0 software was used to analyze the data from relevant studies and to construct a forest plot. Different effect sizes were selected for the meta-analysis. Results In total, 24 publications were included in this meta-analysis. After review of their full-text, 16 articles studied the association between lncRNAs and clinicopathological characteristics, 2 discussing diagnosis and 16 discussing prognosis. Our results showed that overexpression of CCAT1 was significantly correlated with tumor stage (I + II vs III + IV) (OR, 4.99; 95% CI 2.77–8.99; P<0.001) and lymph node metastasis in CCA (OR, 4.75; 95% CI 2.65–8.52; P<0.001). Furthermore, elevated CCAT lncRNA family expression predicted a shorter overall survival (HR, 2.09; 95% CI 1.17–3.00; P<0.001), especially CCAT2. Upregulation of CCAT2 was also obviously associated with tumor stage in CCA (OR, 5.29; 95% CI 2.64–10.58; P=0.001). Conclusion This is the first meta-analysis to assess the relationship between expression of lncRNAs and the clinical values of patients with CCA. lncRNAs can function as potential molecular biomarkers of the clinicopathology and prognosis of CCA.
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Affiliation(s)
- Kangfu Dai
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ; .,Department of HepatoBiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China, ;
| | - Jing Quan
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ;
| | - Fangli Yan
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ;
| | - Xinghan Jin
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ;
| | - Xiang Pan
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ;
| | - Xiaorui Song
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ;
| | - Shijie Zhang
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ;
| | - Qingqi Ren
- Department of HepatoBiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China, ;
| | - Jikui Liu
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ; .,Department of HepatoBiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China, ;
| | - Xiaoping Liu
- Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, P.R. China, ; .,Department of HepatoBiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China, ;
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Jiang F, Ling X. The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development. J Cancer 2019; 10:2407-2414. [PMID: 31258745 PMCID: PMC6584350 DOI: 10.7150/jca.32411] [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: 12/19/2018] [Accepted: 04/18/2019] [Indexed: 02/07/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a malignancy with increasing incidence in recent years. CCA patients are usually diagnosed at advanced stage due to lack of apparent symptoms and specifically diagnostic markers. Nowadays, surgical removal is the only effective method for CCA whereas overall 5-year-survival rate keeps around 10%. Long-noncoding RNA (lncRNA), a subtype of noncoding RNA, is widely studied to be abnormally expressed in multiple cancers including CCA. LncRNA can promote proliferation, migration, invasion and inhibit apoptosis of CCA. Moreover, lncRNA is negatively correlated with the prognosis of CCA. LncRNA may contribute to the development of CCA via modulating gene transcription, sponging microRNA, regulating CCA-related signaling pathways or protein expression. LncRNA is thought to be potential diagnostic markers and therapeutic targets for CCA.
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Qi G, Kong W, Mou X, Wang S. A new method for excavating feature lncRNA in lung adenocarcinoma based on pathway crosstalk analysis. J Cell Biochem 2018; 120:9034-9046. [DOI: 10.1002/jcb.28177] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 11/08/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Guoqiang Qi
- Department of Electronic Engineering College of Information Engineering, Shanghai Maritime University Shanghai China
| | - Wei Kong
- Department of Electronic Engineering College of Information Engineering, Shanghai Maritime University Shanghai China
| | - Xiaoyang Mou
- Department of Biochemistry Rowan University and Guava Medicine Glassboro New Jersey
| | - Shuaiqun Wang
- Department of Electronic Engineering College of Information Engineering, Shanghai Maritime University Shanghai China
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Neve B, Jonckheere N, Vincent A, Van Seuningen I. Epigenetic Regulation by lncRNAs: An Overview Focused on UCA1 in Colorectal Cancer. Cancers (Basel) 2018; 10:cancers10110440. [PMID: 30441811 PMCID: PMC6266399 DOI: 10.3390/cancers10110440] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 11/06/2018] [Accepted: 11/08/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancers have become the second leading cause of cancer-related deaths. In particular, acquired chemoresistance and metastatic lesions occurring in colorectal cancer are a major challenge for chemotherapy treatment. Accumulating evidence shows that long non-coding (lncRNAs) are involved in the initiation, progression, and metastasis of cancer. We here discuss the epigenetic mechanisms through which lncRNAs regulate gene expression in cancer cells. In the second part of this review, we focus on the role of lncRNA Urothelial Cancer Associated 1 (UCA1) to integrate research in different types of cancer in order to decipher its putative function and mechanism of regulation in colorectal cancer cells. UCA1 is highly expressed in cancer cells and mediates transcriptional regulation on an epigenetic level through the interaction with chromatin modifiers, by direct regulation via chromatin looping and/or by sponging the action of a diversity of miRNAs. Furthermore, we discuss the role of UCA1 in the regulation of cell cycle progression and its relation to chemoresistance in colorectal cancer cells.
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Affiliation(s)
- Bernadette Neve
- Inserm UMR-S 1172, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc), Team "Mucins, Epithelial Differentiation and Carcinogenesis"; University Lille; CHU Lille,59045, Lille CEDEX, France.
| | - Nicolas Jonckheere
- Inserm UMR-S 1172, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc), Team "Mucins, Epithelial Differentiation and Carcinogenesis"; University Lille; CHU Lille,59045, Lille CEDEX, France.
| | - Audrey Vincent
- Inserm UMR-S 1172, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc), Team "Mucins, Epithelial Differentiation and Carcinogenesis"; University Lille; CHU Lille,59045, Lille CEDEX, France.
| | - Isabelle Van Seuningen
- Inserm UMR-S 1172, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc), Team "Mucins, Epithelial Differentiation and Carcinogenesis"; University Lille; CHU Lille,59045, Lille CEDEX, France.
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Dysregulation of KCNQ1OT1 promotes cholangiocarcinoma progression via miR-140-5p/SOX4 axis. Arch Biochem Biophys 2018; 658:7-15. [PMID: 30243712 DOI: 10.1016/j.abb.2018.09.019] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 08/21/2018] [Accepted: 09/18/2018] [Indexed: 12/15/2022]
Abstract
It is commonly recognized that aberrant expression of long non-coding RNAs (lncRNAs) is an important cause of cancer progression. The oncogenic property of KCNQ1OT1 has been identified in several malignant tumors. Here, we decided to explore the biological function and molecular mechanism of KCNQ1OT1 in cholangiocarcinoma (CCA). The expression conditions of KCNQ1OT1 in different tissues and cell lines were examined with qRT-PCR analysis. As expected, KCNQ1OT1 was highly expressed in CCA tissues and cell lines. Results of functional assays revealed the oncogenic function of KCNQ1OT in cholangiocarcinoma progression. The positive effect of KCNQ1OT1 on cell proliferation, invasion and epithelial-mesenchymal transition was identified by performing MTT assay, colony formation assay, transwell invasion assay and western blotting. Whereas, the negative effect of KCNQ1OT1 on the cell apoptosis was tested with flow cytometry analysis. Mechanism investigation revealed that KCNQ1OT1 can act as a ceRNA to improve CCA progression by regulating miR-140-5p/SOX4 axis. Recue assays were conducted to demonstrate the actual effects of KCNQ1OT1-miR-140-5p-SOX4 pathway on CCA progression.
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Li B, Li X. Overexpression of hsa_circ_0007534 predicts unfavorable prognosis for osteosarcoma and regulates cell growth and apoptosis by affecting AKT/GSK-3β signaling pathway. Biomed Pharmacother 2018; 107:860-866. [PMID: 30142548 DOI: 10.1016/j.biopha.2018.08.086] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Revised: 08/11/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022] Open
Abstract
Accumulating evidence demonstrated the pivotal roles of circular RNAs (circRNAs) in several types of cancers. However, the study relevant to the biological functions of circRNAs in osteosarcoma (OS) is still very limited. Recently, hsa_circ_0007534 has been proved to play key roles in colorectal carcinoma and glioma. In this study, qRT-PCR was used to determine hsa_circ_0007534 expression in OS tissues and cells. The clinical value of hsa_circ_0007534 was further explored. Additionally, cell growth, clone formation ability and cell apoptosis were assessed after hsa_circ_0007534 silenced. The xenograft study was further induced to investigate the roles of hsa_circ_0007534 in vivo. Moreover, AKT/GSK-3β pathway was measured to illustrate the mechanism of hsa_circ_0007534 exerts in OS progression. The data demonstrated that hsa_circ_0007534 is overexpressed in OS tissue samples and cells and this up-regulation is related with larger tumor size and poorer differentiation degree. Moreover, hsa_circ_0007534 is a dismal prognostic biomarker for OS patients. For the functional assays, knockdown of hsa_circ_0007534 suppresses OS cell growth in vitro and in vivo. In addition, hsa_circ_0007534 protects against cell apoptosis via Bcl-2/caspase-3 pathway. Furthermore, AKT/GSK-3β pathway could be activated by hsa_circ_0007534 to facilitate OS progression. In summary, hsa_circ_0007534 may be a rational predictive marker and therapeutic target for OS.
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Affiliation(s)
- Baoquan Li
- Department of Orthopedics Surgery, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
| | - Xiaoguang Li
- Department of Orthopedics Surgery, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China
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Xing L, Zhang L, Feng Y, Cui Z, Ding L. Downregulation of circular RNA hsa_circ_0001649 indicates poor prognosis for retinoblastoma and regulates cell proliferation and apoptosis via AKT/mTOR signaling pathway. Biomed Pharmacother 2018; 105:326-333. [PMID: 29864621 DOI: 10.1016/j.biopha.2018.05.141] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 05/26/2018] [Accepted: 05/28/2018] [Indexed: 12/17/2022] Open
Abstract
Retinoblastoma (RB) is the most common intraocular malignancy in infants and children with high mortality rate in developing countries. Emerging evidence demonstrated that abnormally expressed circular RNAs (circRNAs) are involved in tumorigenesis and progression in several malignancies. However, their clinical values, biological functions and mechanisms in RB has not been reported before. Recently, hsa_circ_0001649 was found to play imperative roles in cholangiocarcinoma, gastric cancer, and hepatocellular carcinoma. In the current study, qRT-PCR was performed to detect the expression of hsa_circ_0001649 in RB samples and cells. The correlations between hsa_circ_0001649 expression and clinicopathologic characteristics were further analyzed. In addition, we up-regulated hsa_circ_0001649 in Y79 cells and knocked down hsa_circ_0001649 in WERI-Rb1 cells to explore its effect on cell proliferation and apoptosis. The animal study was performed to confirm the in vitro results. Furthermore, AKT/mTOR signaling pathway was detected to clarify the molecular mechanisms of hsa_circ_0001649 exerts in RB cell growth. The results indicated that hsa_circ_0001649 was decreased in RB tissues and cells, and this downregulation was associated with larger tumor size and advanced intraocular international retinoblastoma classify (IIRC) stage in RB patients. Additionally, hsa_circ_0001649 could act as an independent prognostic predictor for overall survival in patients with RB. Moreover, hsa_circ_0001649 inhibits cell growth and promotes cell apoptosis in RB cells. AKT/mTOR signaling pathway is involved in the cell growth alteration affected by hsa_circ_0001649. Overall, hsa_circ_0001649 might be a potentially useful prognostic biomarker and therapeutic target for RB.
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Affiliation(s)
- Lichen Xing
- Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China
| | - Leiming Zhang
- Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China
| | - Yali Feng
- Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China
| | - Zhe Cui
- Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China
| | - Lin Ding
- Department of Clinical Skills Experimental Teaching Center, Qiqihar Medical University, Heilongjiang Province, 161000, China.
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Tang RX, Chen ZM, Zeng JJ, Chen G, Luo DZ, Mo WJ. Clinical implication of UCA1 in non-small cell lung cancer and its effect on caspase-3/7 activation and apoptosis induction in vitro. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:2295-2304. [PMID: 31938341 PMCID: PMC6958301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 03/26/2018] [Indexed: 06/10/2023]
Abstract
Since urothelial cancer associated 1 (UCA1) was discovered in human bladder cancer, it has been reported to be dysregulated expressed in various kinds of solid tumors. But the clinical role and the function of UCA1 in non-small cell lung cancer (NSCLC) remains incompletely understood. In this study, we mined the data of UCA1 expression in NSCLC from Oncomine, Gene expression profiling interactive analysis (GEPIA) and cBioPortal to analyze the contribution of UCA1 in the cancer initiation and progression of NSCLC. We also performed a series of in vitro experiments by using NSCLC cells to confirm the biological function of UCA1 in NSCLC, especially its effect on caspase-3/7 activity and apoptosis through RNA interference experiment. From Oncomine, the UCA1 levels were both up-regulated in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC), as compared to non-cancerous controls. Higher levels of UCA1 pointed to a poorer overall survival in NSCLC, with the HR being 1.3. Only two genetic alterations, including amplification and deep deletion, were observed for UCA1 as provided by cBioPortal. Both MTS and Cell Titer-blue assays showed an accordant inhibitory effect of UCA1 siRNAs on the cell growth. In conclusion, lncRNA UCA1 might play a substantial role in the occurrence and development of NSCLC, especially in LUAD patients, which is partly due to its effect on caspase-3/7 activity suppression.
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Affiliation(s)
- Rui-Xue Tang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Zhi-Min Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jing-Jing Zeng
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Gang Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Dian-Zhong Luo
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Wei-Jia Mo
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
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Guo L, Zhou Y, Chen Y, Sun H, Wang Y, Qu Y. LncRNA ASAP1-IT1 positively modulates the development of cholangiocarcinoma via hedgehog signaling pathway. Biomed Pharmacother 2018; 103:167-173. [PMID: 29653361 DOI: 10.1016/j.biopha.2018.04.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 03/29/2018] [Accepted: 04/02/2018] [Indexed: 12/15/2022] Open
Abstract
Over the past decades, lncRNAs have attracted more and more attentions of researchers. It has been verified that lncRNAs can modulate multiple biological behaviors in various human cancers. LncRNA ASAP1-IT1 has been certified to be a tumor facilitator in several malignant tumors. This study aims to investigate the effects of dysregulated ASAP1-IT1 on biological processes of Cholangiocarcinoma. The high expression level of ASAP1-IT1 was tested in Cholangiocarcinoma tissues and cells with qRT-PCR. Upregulation of ASAP1-IT predicted the unfavorable prognosis for Cholangiocarcinoma patients. Next, ASAP1-IT1 was knocked down in cancerous cells for loss-of function assay. MTT, colony formation and transwell and western bot assays were performed to demonstrate the specific impacts of ASAP1-IT1 on proliferation, migration and EMT progression of Cholangiocarcinoma. Cells. As a results, the Cholangiocarcinoma progression was inhibited. Hedgehog signaling pathway has been discovered to be a treatment target in Cholangiocarcinoma. In this study, the interaction between ASAP1-IT1 and hedgehog pathway was specifically investigated. Smo and Gli1, two hedgehog-related proteins were examined in Cholangiocarcinoma cells. The results of qRT-PCR and western blot assay suggested that ASAP1-IT1 could positively modulate Smo and Gli1 in Cholangiocarcinoma. Finally, rescue assays were carried out to prove that ASAP1-IT1 could improve Cholangiocarcinoma progression and development via hedgehog signaling pathway.
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Affiliation(s)
- Linqi Guo
- Department of General surgery, First Affiliated Hospital of Jiamusi University, Jiamusi City 154003, China
| | - Yu Zhou
- Department of Tumor surgery, First Affiliated Hospital of Jiamusi University, Jiamusi City 154003, China
| | - Ying Chen
- Department of Critical care medicine, First Affiliated Hospital of Jiamusi University, Jiamusi City 154003, China
| | - Huawei Sun
- Department of Radiochemotherapy, First Affiliated Hospital of Jiamusi University, Jiamusi City 154003, China
| | - Yue Wang
- Department of pharmacology and toxicology, Wright State University, Fairborn, OH, 45435, USA
| | - Yikun Qu
- Department of General surgery, First Affiliated Hospital of Jiamusi University, Jiamusi City 154003, China.
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Xu Y, Yao Y, Jiang X, Zhong X, Wang Z, Li C, Kang P, Leng K, Ji D, Li Z, Huang L, Qin W, Cui Y. SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2018; 37:81. [PMID: 29642935 PMCID: PMC5896100 DOI: 10.1186/s13046-018-0747-x] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 04/02/2018] [Indexed: 01/10/2023]
Abstract
Background Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) behave as a novel class of transcription products during multiple cancer processes. However, the mechanisms responsible for their alteration in cholangiocarcinoma (CCA) are not fully understood. Methods The expression of SPRY4-IT1 in CCA tissues and cell lines was determined by RT-qPCR, and the association between SPRY4-IT1 transcription and clinicopathologic features was analyzed. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of SPRY4-IT1 and activate its transcription. The biological function of SPRY4-IT1 in CCA cells was evaluated both in vitro and in vivo. ChIP, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays were performed to determine the molecular mechanism of SPRY4-IT1 in cell proliferation, apoptosis and invasion. Results SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p. Conclusions Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. Electronic supplementary material The online version of this article (10.1186/s13046-018-0747-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yi Xu
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Yue Yao
- Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Xingming Jiang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Xiangyu Zhong
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Zhidong Wang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Chunlong Li
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Pengcheng Kang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Kaiming Leng
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Daolin Ji
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Zhenglong Li
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Lining Huang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Wei Qin
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China
| | - Yunfu Cui
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China.
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Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095. Biochem Biophys Res Commun 2018; 496:712-718. [PMID: 29360452 DOI: 10.1016/j.bbrc.2018.01.109] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 01/16/2018] [Indexed: 11/22/2022]
Abstract
The long non-coding RNA SNHG7 (small nucleolar RNA host gene 7) has been reported to be involved in various cancers as a potential oncogene. However, the functions and molecular mechanisms of SNHG7 in glioblastoma (GBM) are largely unknown. In the present study, we showed that the expression of SNHG7 was significantly upregulated in GBM tissues and cell lines compared with non-cancerous brain tissues. Furthermore, we found that SNHG7 knockdown remarkably suppressed the proliferation, migration and invasion of A172 and U87 cells while inducing their apoptosis. Subsequently, we showed that SNHG7 knockdown significantly inhibited tumor growth and metastasis in vivo by using xenograft experiments in nude mice. In terms of mechanism, we found that SNHG7 directly inhibited miR-5095, which targeted the 3' UTR of CTNNB1 mRNA and subsequently downregulated the Wnt/β-catenin signaling pathway in GBM. Using rescue experiments, we demonstrated that SNHG7 promoted the proliferation, migration and invasion of GBM cells through the inhibition of miR-5095 and concomitant activation of Wnt/β-catenin signaling pathway. Taken together, the SNHG7/miR-5095 axis might be a potential target for the development of effective GBM therapy.
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