|
1
|
Ghorbani A, Hosseinie F, Khorshid Sokhangouy S, Islampanah M, Khojasteh-Leylakoohi F, Maftooh M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Nazari E, Avan A. The prognostic, diagnostic, and therapeutic impact of Long noncoding RNAs in gastric cancer. Cancer Genet 2024; 282-283:14-26. [PMID: 38157692 DOI: 10.1016/j.cancergen.2023.12.006] [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: 05/28/2023] [Revised: 11/27/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.
Collapse
Affiliation(s)
- Atousa Ghorbani
- Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Hosseinie
- Department of Nursing, Faculty of Nursing and Midwifery, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Saeideh Khorshid Sokhangouy
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Muhammad Islampanah
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Nazari
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
2
|
Du J, Su Y, Gao J, Tai Y. The expression and function of long noncoding RNAs in hepatocellular carcinoma. CANCER INNOVATION 2023; 2:488-499. [PMID: 38125766 PMCID: PMC10730004 DOI: 10.1002/cai2.90] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/23/2023] [Accepted: 07/07/2023] [Indexed: 12/23/2023]
Abstract
With the deepening of the genome project study, attention on noncoding RNAs is increasing. Long noncoding RNAs (lncRNAs) have become a new research hotspot. A growing number of studies have revealed that lncRNAs are involved in tumorigenesis and tumor suppressor pathways. Aberrant expressions of lncRNAs have been found in a variety of human tumors including hepatocellular carcinoma (HCC). In this review, we provide a brief introduction to lncRNA and highlight recent research on the functions and clinical significance of lncRNAs in HCC.
Collapse
Affiliation(s)
- Jingli Du
- Senior Department of TuberculosisThe 8th Medical Center of PLA General HospitalBeijingChina
| | - Yue Su
- Senior Department of TuberculosisThe 8th Medical Center of PLA General HospitalBeijingChina
| | - Jianzhi Gao
- Department of OncologyZhuozhou Hospital, ZhuozhouHebeiChina
| | - Yanhong Tai
- Department of PathologyThe 5th Medical Center of PLA General HospitalBeijingChina
| |
Collapse
|
|
3
|
de Oliveira JC. Transcribed Ultraconserved Regions: New regulators in cancer signaling and potential biomarkers. Genet Mol Biol 2023; 46:e20220125. [PMID: 36622962 PMCID: PMC9829027 DOI: 10.1590/1678-4685-gmb-2022-0125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 11/06/2022] [Indexed: 01/11/2023] Open
Abstract
The ultraconserved regions (UCRs) are 481 genomic elements, longer than 200 bp, 100% conserved in human, mouse, and rat genomes. Usually, coding regions are more conserved, but more than 80% of UCRs are either intergenic or intronic, and many of them produce long non-coding RNAs (lncRNAs). Recently, the deregulated expression of transcribed UCRs (T-UCRs) has been associated with pathological conditions. But, differently from many lncRNAs with recognized crucial effects on malignant cell processes, the role of T-UCRs in the control of cancer cell networks is understudied. Furthermore, the potential utility of these molecules as molecular markers is not clear. Based on this information, the present review aims to organize information about T-UCRs with either oncogenic or tumor suppressor role associated with cancer cell signaling, and better describe T-UCRs with potential utility as prognosis markers. Out of 481 T-UCRs, 297 present differential expression in cancer samples, 23 molecules are associated with tumorigenesis processes, and 12 have more clear potential utility as prognosis markers. In conclusion, T-UCRs are deregulated in several tumor types, highlighted as important molecules in cancer networks, and with potential utility as prognosis markers, although further investigation for translational medicine is still needed.
Collapse
|
|
4
|
Bozgeyik I, Ege B, Koparal M, Yumrutas O. Non-coding RNAs transcribed from ultra-conserved regions (T-UCRs) are differentially expressed in dental follicle tissues of impacted mandibular third molars. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2022; 123:271-275. [PMID: 35477012 DOI: 10.1016/j.jormas.2022.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/07/2022] [Accepted: 04/20/2022] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Transcribed ultra-conserved regions (T-UCRs) are a new class of long non-coding RNA molecules transcribed from ultra-conserved regions (UCRs) of the human genome. T-UCRs are extremely conserved in the human, rat, and mouse genomes. Deletions of genomic areas containing UCRs resulted in live mice that developed without discernible phenotypes, implying that T-UCRs are involved in developmental processes. In addition, there is increasing evidence that dental follicle tissues exhibit various cellular alterations involving deregulation of protein-coding genes and non-coding RNAs. Accordingly, the main objective of the present study was to determine the clinical significance and distinct expression signatures of non-coding RNA molecules transcribed from ultra-conserved regions in dental follicle samples. MATERIALS AND METHODS From March 2021 to December 2022, a total 42 patients who referred to clinic of oral and maxillofacial surgery department with the indications of impacted mandibular third molar extraction from 38th and 48th positions were enrolled for the study. For the analysis of T-UCR expression levels, real-time quantitative reverse transcription PCR method was used. RESULTS Findings of the present study indicated that T-UCRs are distinctly expressed in dental follicle tissues of impacted mandibular third molars. The expression of uc.38, uc.112, and uc.338 was found to be significantly increased in the dental follicles of impacted mandibular third molars, indicating a clinical significance of these molecules. In addition, no differences in T-UCR expression were found as a function of demographic factors. CONCLUSIONS Collectively, transcribed ultra-conserved elements, such as uc.38, uc.112, and uc.338, are considerably deregulated in the dental follicle tissues of impacted mandibular third molars and might be responsible for the molecular changes acquired by dental follicle tissues of impacted mandibular third molars.
Collapse
Affiliation(s)
- Ibrahim Bozgeyik
- Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.
| | - Bilal Ege
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Adiyaman University, Adiyaman, Turkey.
| | - Mahmut Koparal
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Adiyaman University, Adiyaman, Turkey.
| | - Onder Yumrutas
- Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.
| |
Collapse
|
|
5
|
Li Z, Jiang L, Zhang Z, Deng M, Wei W, Tang H, Guo S, Ye Y, Yao K, Liu Z, Zhou F. Long noncoding RNAs to predict postoperative recurrence in bladder cancer and to develop a new molecular classification system. Cancer Med 2021; 11:539-552. [PMID: 34816620 PMCID: PMC8729057 DOI: 10.1002/cam4.4443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 10/06/2021] [Accepted: 10/28/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Reliable molecular markers are much needed for early prediction of recurrence in muscle-invasive bladder cancer (MIBC) patients. We aimed to build a long-noncoding RNA (lncRNA) signature to improve recurrence prediction and lncRNA-based molecular classification of MIBC. METHODS LncRNAs of 320 MIBC patients from the Cancer Genome Atlas (TCGA) database were analyzed, and a nomogram was established. A molecular classification system was created, and immunotherapy and chemotherapy response predictions, immune score analysis, immune infiltration analysis, and mutational data analysis were conducted. Survival analysis validation was also performed. RESULTS An eight-lncRNA signature classifed the patients into high- and low-risk subgroups, and these groups had significantly different (disease-free survival) DFS. The ability of the eight-lncRNA signature to make an accurate prognosis was tested using a validation dataset from our samples. The nomogram achieved a C-index of 0.719 (95% CI, 0.674-0.764). Time-dependent receiver operating characteristic curve (ROC) analysis indicated the superior prognostic accuracy of nomograms for DFS prediction (0.76, 95% CI, 0.697-0.807). Further, the four clusters (median DFS = 11.8, 15.3, 17.9, and 18.9 months, respectively) showed a high frequency of TTN (cluster 1), fibroblast growth factor receptor-3 (cluster 2), TP53 (cluster 3), and TP53 mutations (cluster 4), respectively. They were enriched with M2 macrophages (cluster 1), CD8+ T cells (cluster 2), M0 macrophages (cluster 3), and M0 macrophages (cluster 4), respectively. Clusters 2 and 3 demonstrated potential sensitivity to immunotherapy and insensitivity to chemotherapy, whereas cluster 4 showed potential insensitivity to immunotherapy and sensitivity to chemotherapy. CONCLUSIONS The eight-lncRNA signature risk model may be a reliable prognostic signature for MIBC, which provides new insights into prediction of recurrence of MIBC. The model may help clinical decision and eventually benefit patients.
Collapse
Affiliation(s)
- Zhiyong Li
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lijuan Jiang
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhiling Zhang
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Minhua Deng
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wensu Wei
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Huancheng Tang
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shengjie Guo
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yunlin Ye
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Kai Yao
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhuowei Liu
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Fangjian Zhou
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| |
Collapse
|
|
6
|
Soler M, Davalos V, Sánchez-Castillo A, Mora-Martinez C, Setién F, Siqueira E, Castro de Moura M, Esteller M, Guil S. The transcribed ultraconserved region uc.160+ enhances processing and A-to-I editing of the miR-376 cluster: hypermethylation improves glioma prognosis. Mol Oncol 2021; 16:648-664. [PMID: 34665919 PMCID: PMC8807354 DOI: 10.1002/1878-0261.13121] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 10/01/2021] [Accepted: 10/15/2021] [Indexed: 11/11/2022] Open
Abstract
Transcribed ultraconserved regions (T‐UCRs) are noncoding RNAs derived from DNA sequences that are entirely conserved across species. Their expression is altered in many tumor types, and, although a role for T‐UCRs as regulators of gene expression has been proposed, their functions remain largely unknown. Herein, we describe the epigenetic silencing of the uc.160+ T‐UCR in gliomas and mechanistically define a novel RNA–RNA regulatory network in which uc.160+ modulates the biogenesis of several members of the miR‐376 cluster. This includes the positive regulation of primary microRNA (pri‐miRNA) cleavage and an enhanced A‐to‐I editing on its mature sequence. As a consequence, the expression of uc.160+ affects the downstream, miR‐376‐regulated genes, including the transcriptional coregulators RING1 and YY1‐binding protein (RYBP) and forkhead box P2 (FOXP2). Finally, we elucidate the clinical impact of our findings, showing that hypermethylation of the uc.160+ CpG island is an independent prognostic factor associated with better overall survival in lower‐grade gliomas, highlighting the importance of T‐UCRs in cancer pathophysiology.
Collapse
Affiliation(s)
- Marta Soler
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain
| | - Veronica Davalos
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain
| | - Anaís Sánchez-Castillo
- Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands
| | - Carlos Mora-Martinez
- Centre of Excellence in Experimental and Computational Developmental Biology, Institute of Biotechnology, University of Helsinki, Finland
| | - Fernando Setién
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain
| | - Edilene Siqueira
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain.,Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), Brasilia, Brazil
| | | | - Manel Esteller
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain.,Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.,Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.,Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Spain
| | - Sonia Guil
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain.,Germans Trias i Pujol Health Science Research Institute, Barcelona, Spain
| |
Collapse
|
|
7
|
Pereira Zambalde E, Bayraktar R, Schultz Jucoski T, Ivan C, Rodrigues AC, Mathias C, knutsen E, Silveira de Lima R, Fiori Gradia D, de Souza Fonseca Ribeiro EM, Hannash S, Adrian Calin G, Carvalhode Oliveira J. A novel lncRNA derived from an ultraconserved region: lnc- uc.147, a potential biomarker in luminal A breast cancer. RNA Biol 2021; 18:416-429. [PMID: 34387142 PMCID: PMC8677017 DOI: 10.1080/15476286.2021.1952757] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 06/02/2021] [Accepted: 07/04/2021] [Indexed: 02/06/2023] Open
Abstract
The human genome contains 481 ultraconserved regions (UCRs), which are genomic stretches of over 200 base pairs conserved among human, rat, and mouse. The majority of these regions are transcriptionally active (T-UCRs), and several have been found to be differentially expressed in tumours. Some T-UCRs have been functionally characterized, but of those few have been associated to breast cancer (BC). Using TCGA data, we found 302 T-UCRs related to clinical features in BC: 43% were associated with molecular subtypes, 36% with oestrogen-receptor positivity, 17% with HER2 expression, 12% with stage, and 10% with overall survival. The expression levels of 12 T-UCRs were further analysed in a cohort of 82 Brazilian BC patients using RT-qPCR. We found that uc.147 is high expressed in luminal A and B patients. For luminal A, a subtype usually associated with better prognosis, high uc.147 expression was associated with a poor prognosis and suggested as an independent prognostic factor. The lncRNA from uc.147 (lnc-uc.147) is located in the nucleus. Northern blotting results show that uc.147 is a 2,8 kb monoexonic trancript, and its sequence was confirmed by RACE. The silencing of uc.147 increases apoptosis, arrests cell cycle, and reduces cell viability and colony formation in BC cell lines. Additionally, we identifed 19 proteins that interact with lnc-uc.147 through mass spectrometry and demonstrated a high correlation of lnc-uc.147 with the neighbour gene expression and miR-18 and miR-190b. This is the first study to analyse the expression of all T-UCRs in BC and to functionally assess the lnc-uc.147.
Collapse
Affiliation(s)
- Erika Pereira Zambalde
- Laboratory of Human Cytogenetics and Oncogenetics, Department of Genetics, Universidade Federal Do Paraná, Curitiba, PR, Brazil
- Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
| | - Recep Bayraktar
- Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
| | - Tayana Schultz Jucoski
- Laboratory of Human Cytogenetics and Oncogenetics, Department of Genetics, Universidade Federal Do Paraná, Curitiba, PR, Brazil
| | - Cristina Ivan
- Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ana Carolina Rodrigues
- Laboratory of Human Cytogenetics and Oncogenetics, Department of Genetics, Universidade Federal Do Paraná, Curitiba, PR, Brazil
| | - Carolina Mathias
- Laboratory of Human Cytogenetics and Oncogenetics, Department of Genetics, Universidade Federal Do Paraná, Curitiba, PR, Brazil
| | - Erik knutsen
- Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
- Department of Medical Biology, Faculty of Health Sciences, UiT - the Arctic University of Norway, Tromsø, Norway
| | | | - Daniela Fiori Gradia
- Laboratory of Human Cytogenetics and Oncogenetics, Department of Genetics, Universidade Federal Do Paraná, Curitiba, PR, Brazil
| | | | - Samir Hannash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George Adrian Calin
- Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
- Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaqueline Carvalhode Oliveira
- Laboratory of Human Cytogenetics and Oncogenetics, Department of Genetics, Universidade Federal Do Paraná, Curitiba, PR, Brazil
| |
Collapse
|
|
8
|
Li G, Gong J, Cao S, Wu Z, Cheng D, Zhu J, Huang X, Tang J, Yuan Y, Cai W, Zhang H. The Non-Coding RNAs Inducing Drug Resistance in Ovarian Cancer: A New Perspective for Understanding Drug Resistance. Front Oncol 2021; 11:742149. [PMID: 34660304 PMCID: PMC8514763 DOI: 10.3389/fonc.2021.742149] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/10/2021] [Indexed: 12/30/2022] Open
Abstract
Ovarian cancer, a common malignant tumor, is one of the primary causes of cancer-related deaths in women. Systemic chemotherapy with platinum-based compounds or taxanes is the first-line treatment for ovarian cancer. However, resistance to these chemotherapeutic drugs worsens the prognosis. The underlying mechanism of chemotherapeutic resistance in ovarian cancer remains unclear. Non-coding RNAs, including long non-coding RNAs, microRNAs, and circular RNAs, have been implicated in the development of drug resistance. Abnormally expressed non-coding RNAs can promote ovarian cancer resistance by inducing apoptosis inhibition, protective autophagy, abnormal tumor cell proliferation, epithelial-mesenchymal transition, abnormal glycolysis, drug efflux, and cancer cell stemness. This review summarizes the role of non-coding RNAs in the development of chemotherapeutic resistance in ovarian cancer, including their mechanisms, targets, and potential signaling pathways. This will facilitate the development of novel chemotherapeutic agents that can target these non-coding RNAs and improve ovarian cancer treatment.
Collapse
Affiliation(s)
- Gaofeng Li
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Jun Gong
- Department of Abdominal and Pelvic Medical Oncology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China
| | - Shulong Cao
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Zhaoyang Wu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Dong Cheng
- Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Zhu
- Hubei Enshi College, Enshi, China
| | - Xuqun Huang
- Department of Thoracic Medical Oncology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China
| | - Jingyi Tang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Yuning Yuan
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Wenqi Cai
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Haiyuan Zhang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| |
Collapse
|
|
9
|
Zhang M, Zhou J, Jiao L, Xu L, Hou L, Yin B, Qiang B, Lu S, Shu P, Peng X. Long Non-coding RNA T-uc.189 Modulates Neural Progenitor Cell Fate by Regulating Srsf3 During Mouse Cerebral Cortex Development. Front Neurosci 2021; 15:709684. [PMID: 34354569 PMCID: PMC8329457 DOI: 10.3389/fnins.2021.709684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/28/2021] [Indexed: 11/29/2022] Open
Abstract
Neurogenesis is a complex process that depends on the delicate regulation of spatial and temporal gene expression. In our previous study, we found that transcribed ultra-conserved regions (T-UCRs), a class of long non-coding RNAs that contain UCRs, are expressed in the developing nervous systems of mice, rhesus monkeys, and humans. In this study, we first detected the full-length sequence of T-uc.189, revealing that it was mainly concentrated in the ventricular zone (VZ) and that its expression decreased as the brain matured. Moreover, we demonstrated that knockdown of T-uc.189 inhibited neurogenesis. In addition, we found that T-uc.189 positively regulated the expression of serine-arginine-rich splicing factor 3 (Srsf3). Taken together, our results are the first to demonstrate that T-uc.189 regulates the expression of Srsf3 to maintain normal neurogenesis during cortical development.
Collapse
Affiliation(s)
- Meng Zhang
- Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China
| | - Junjie Zhou
- The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Jiao
- Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China
| | - Longjiang Xu
- Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China
| | - Lin Hou
- The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bin Yin
- The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Boqin Qiang
- The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuaiyao Lu
- Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China
| | - Pengcheng Shu
- The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaozhong Peng
- Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China.,The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
10
|
Wang Y, Zhou D, Feng Y, Chen G, Li N. T-UCRs with digestive and respiratory diseases. Bioorg Med Chem Lett 2020; 30:127306. [PMID: 32631526 DOI: 10.1016/j.bmcl.2020.127306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/31/2020] [Accepted: 06/01/2020] [Indexed: 12/23/2022]
Abstract
From the perspective of histoembryology, the lung, gaster, and intestines that derived from the endoderm of the gastrula are structurally homologous. The interplay of intestines and lung in many pathologic changes is called the gut-lung axis. RNAs transcribed from ultraconserved regions (T-UCRs) are highly evolutionarily conserved in many mammalian genomes and have been found to be important in the pathogenesis and diagnosis of many diseases. More and more studies in recent years have shown that T-UCRs play important roles both in digestive and respiratory diseases. Taking the gut-lung axis as the entry point, this review summarizes the T-UCRs related to digestive and respiratory diseases in recent years. Meanwhile, these T-UCRs and their targets can lay a foundation for future drug research.
Collapse
Affiliation(s)
- Yajun Wang
- School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Di Zhou
- School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yuan Feng
- School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Gang Chen
- School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug, Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Ning Li
- School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug, Shenyang Pharmaceutical University, Shenyang 110016, China.
| |
Collapse
|
|
11
|
Pereira Zambalde E, Mathias C, Rodrigues AC, Souza Fonseca Ribeiro EM, Fiori Gradia D, Calin GA, Carvalho de Oliveira J. Highlighting transcribed ultraconserved regions in human diseases. WILEY INTERDISCIPLINARY REVIEWS-RNA 2019; 11:e1567. [DOI: 10.1002/wrna.1567] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 08/02/2019] [Accepted: 08/13/2019] [Indexed: 12/18/2022]
Affiliation(s)
| | - Carolina Mathias
- Department of Genetics Universidade Federal do Paraná Curitiba Brazil
| | | | | | | | - George A. Calin
- Department of Experimental Therapeutics, MD Anderson Cancer Center University of Texas Houston Texas
| | | |
Collapse
|
|
12
|
A long non-coding RNA signature to improve prognostic prediction in clear cell renal cell carcinoma. Biomed Pharmacother 2019; 118:109079. [PMID: 31351427 DOI: 10.1016/j.biopha.2019.109079] [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: 04/03/2019] [Revised: 05/31/2019] [Accepted: 06/02/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Accumulating research reports have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in many types of cancers. However, few lncRNA signatures for predicting cancer prognosis have been established. Our goal is to establish a lncRNA signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC). METHODS We downloaded KIRC lncRNA FPKM (Fragments Per Kilobase of transcript per Million Fragments) standardized expression data from The Cancer Genome Atlas (TCGA) by using the TANRIC tool. We established an 11-lncRNA signature that was clearly linked to the overall survival (OS) rates in the training and test sets. RESULTS The training set was divided into the high-risk and low-risk subgroups, between which the OS was disparate (HR = 1.51, 95%CI = 1.39-1.64, P < 0.0001). The accuracy of the 11-lncRNA signature for predicting prognosis was confirmed in the test set. Further analysis revealed that the prognostic value of this signature was independent of the neoplasm grade and TNM stage. Gene set enrichment analysis (GSEA) was performed, and a summary of 4 gene sets related to canonical pathway, biological process, molecular function and cellular component was obtained. We demonstrated the biological function of these lncRNAs in ccRCC cell lines and found that LINC00488 and HOTTIP promoted tumour proliferation and inhibited apoptosis. However, LINC-PINT had the opposite effect. CONCLUSIONS The establishment of the 11-lncRNA signature indicated the underlying biochemical functional roles of the selected lncRNAs in ccRCC. Our results may provide a reliable theoretical basis for clinical evaluation of ccRCC prognosis.
Collapse
|
|
13
|
LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years. Appl Microbiol Biotechnol 2019; 103:4649-4677. [PMID: 31062053 DOI: 10.1007/s00253-019-09837-5] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 04/07/2019] [Accepted: 04/08/2019] [Indexed: 12/15/2022]
Abstract
Long noncoding RNA (lncRNA) is a kind of RNAi molecule composed of hundreds to thousands of nucleotides. There are several major types of functional lncRNAs which participate in some important cellular pathways. LncRNA-RNA interaction controls mRNA translation and degradation or serves as a microRNA (miRNA) sponge for silencing. LncRNA-protein interaction regulates protein activity in transcriptional activation and silencing. LncRNA guide, decoy, and scaffold regulate transcription regulators of enhancer or repressor region of the coding genes for alteration of expression. LncRNA plays a role in cellular responses including the following activities: regulation of chromatin structural modification and gene expression for epigenetic and cell function control, promotion of hematopoiesis and maturation of immunity, cell programming in stem cell and somatic cell development, modulation of pathogen infection, switching glycolysis and lipid metabolism, and initiation of autoimmune diseases. LncRNA, together with miRNA, are considered the critical elements in cancer development. It has been demonstrated that tumorigenesis could be driven by homeostatic imbalance of lncRNA/miRNA/cancer regulatory factors resulting in biochemical and physiological alterations inside the cells. Cancer-driven lncRNAs with other cellular RNAs, epigenetic modulators, or protein effectors may change gene expression level and affect the viability, immortality, and motility of the cells that facilitate cancer cell cycle rearrangement, angiogenesis, proliferation, and metastasis. Molecular medicine will be the future trend for development. LncRNA/miRNA could be one of the potential candidates in this category. Continuous studies in lncRNA functional discrepancy between cancer cells and normal cells and regional and rational genetic differences of lncRNA profiles are critical for clinical research which is beneficial for clinical practice.
Collapse
|
|
14
|
Tian Y, Feng Y. Up-regulation of long noncoding RNA uc.338 predicts poor survival in non-small cell lung cancer. Cancer Biomark 2018; 22:781-785. [PMID: 29843223 DOI: 10.3233/cbm-181331] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Long noncoding RNA ultraconserved element 338 (uc.338) is a long non-coding RNA reported to function as a promoter in non-small cell lung cancer (NSCLC). However, the function and potential mechanism of uc.338 in NSCLC is still unclear. OBJECTIVE The aim of the present study was to assess the effect of uc.338 on the prognosis of patients with NSCLC. METHODS The expression levels of uc.338 in NSCLC tissues and matched normal lung tissues were examined by real-time quantitative PCR. Then the association between uc.338 levels with clinical variables as well as survival time was investigated. RESULTS We found that uc.338 expression levels were significantly upregulated in NSCLC compared with the matched noncancerous lung tissues (P< 0.01). In addition, increased uc.338 expression was significantly associated with TNM stage (P< 0.003), lymph node metastasis (P< 0.006) and distant metastasis (P< 0.002). More importantly, Kaplan-Meier survival analysis demonstrated that higher uc.338 expression levels were associated with a shorter overall survival (P< 0.0016) and disease-free survival (p< 0.0001) in NSCLC patients. Finally, univariate and multivariate Cox regression analyses revealed that uc.338 was an independent risk factor for overall survival and disease-free survival. CONCLUSIONS Our results show that uc.338 may play an important role in tumorigenesis and progression and could serve as a potential independent prognostic biomarker for patients with NSCLC.
Collapse
|
|
15
|
Zhou J, Wang C, Gong W, Wu Y, Xue H, Jiang Z, Shi M. uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non-Small-Cell Lung Cancer. MOLECULAR THERAPY. NUCLEIC ACIDS 2018; 12:174-183. [PMID: 30195756 PMCID: PMC6023848 DOI: 10.1016/j.omtn.2018.05.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 04/30/2018] [Accepted: 05/07/2018] [Indexed: 01/18/2023]
Abstract
Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding capacity. Previous studies showed that T-UCRs serve as novel oncogenes, or tumor suppressors are involved in tumorigenesis and cancer progressive. Nevertheless, the clinicopathologic significance and regulatory mechanism of T-UCRs in lung cancer (LC) remain largely unknown. We found that uc.454 was downregulated in both non-small-cell LC (NSCLC) tissues and LC cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages. Transfection with uc.454 markedly induced apoptosis and inhibited cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Above results suggested that uc.454 played a suppressive role in LC. Heat shock protein family A member 12B (HSPA12B) protein was negatively regulated by uc.454 at the posttranscriptional level by dual-luciferase reporter assay and affected the expressions of Bcl-2 family members, which finally induced LC apoptosis. The uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms involved in tumor apoptosis, which may potentially serve as a therapeutic target for lung carcinoma.
Collapse
Affiliation(s)
- Jun Zhou
- Department of Respiratory Medicine, The 2nd Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215004, China; Department of Respiratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou 225009, China
| | - Chenghai Wang
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou 225009, China
| | - Weijuan Gong
- Department of Molecular Immunology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou 225009, China
| | - Yandan Wu
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou 225009, China
| | - Huimin Xue
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou 225009, China
| | - Zewei Jiang
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou 225009, China
| | - Minhua Shi
- Department of Respiratory Medicine, The 2nd Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215004, China.
| |
Collapse
|
|
16
|
Zhang HF, Li W, Han YD. LINC00261 suppresses cell proliferation, invasion and Notch signaling pathway in hepatocellular carcinoma. Cancer Biomark 2018; 21:575-582. [PMID: 29278875 DOI: 10.3233/cbm-170471] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Recent findings have identified thousands of long non-coding RNAs (lncRNAs) and reveal that lncRNAs play crucial roles in the regulation of tumor development and progression. However, the clinical significance and potentially functional value of LINC00261 in hepatocellular carcinoma (HCC) remain unknown. METHODS Expression of LINC00261 was detected by qRT-PCR in HCC tissues and adjacent normal tissues. Kaplan-Meier analysis was used to assess the relationship between LINC00261 expression and the overall survival (OS) time. Cell proliferation and invasion were evaluated using MTT assay, cell colony formation assay and transwell assay. The protein expression was determined by western blot analysis. RESULTS In present study, we confirmed that LINC00261 was frequently lower in HCC tissues compared to adjacent normal tissues. Decreased LINC00261 expression associated with lager tumor size, TNM stage (III-IV) and poor overall survival time of HCC patients. The functional assays demonstrated that overexpression of LINC00261 in HCC cells inhibited cell proliferation, cell colony formation, cell invasion and EMT process in vitro. Moreover, we also demonstrated that upregulation of LINC00261 significantly inhibited Notch signaling by downregulating Notch1 and Hes-1 expression in HCC cells. CONCLUSION These results indicated that LINC00261 may be a potential target of HCC treatment.
Collapse
|
|
17
|
Peng L, Yuan XQ, Zhang CY, Peng JY, Zhang YQ, Pan X, Li GC. The emergence of long non-coding RNAs in hepatocellular carcinoma: an update. J Cancer 2018; 9:2549-2558. [PMID: 30026854 PMCID: PMC6036883 DOI: 10.7150/jca.24560] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 03/31/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) accounting for roughly 90% of all primary liver neoplasms is the sixth most frequent neoplasm and the second prominent reason of tumor fatality worldwide. As regulators of diverse biological processes, long non-coding RNAs (lncRNAs) are involved in onset and development of neoplasms. With the continuous booming of well-featured lncRNAs in HCC from 2016 to now, we reviewed the newly-presented comprehension about the relationship between lncRNAs and HCC in this study. To be specific, we summarized the overview function and study tools of lncRNAs, elaborated the roles of lncRNAs in HCC, and sketched the molecule mechanisms of lncRNAs in HCC. In addition, the application of lncRNAs serving as biomarkers in early diagnosis and outcome prediction of HCC patients was highlighted.
Collapse
Affiliation(s)
- Li Peng
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Xiao-Qing Yuan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Chao-Yang Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Jiang-Yun Peng
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Ya-Qin Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Xi Pan
- Department of Oncology, the third Xiangya Hospital, Central South University, Changsha 410013, P.R. China
| | - Guan-Cheng Li
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| |
Collapse
|
|
18
|
El Khodiry A, Afify M, El Tayebi HM. Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis. World J Gastroenterol 2018; 24:549-572. [PMID: 29434445 PMCID: PMC5799857 DOI: 10.3748/wjg.v24.i5.549] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 01/17/2018] [Accepted: 01/23/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs (lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of mRNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.
Collapse
Affiliation(s)
- Aya El Khodiry
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| | - Menna Afify
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| | - Hend M El Tayebi
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| |
Collapse
|
|
19
|
Wang L, Wang XC, Li X, Gu Y, Zhou J, Jiang S, Liu J, Wu C, Ding Z, Wan Y, Wang C. Expression of uc.189 and its clinicopathologic significance in gynecological cancers. Oncotarget 2017; 9:7453-7463. [PMID: 29484123 PMCID: PMC5800915 DOI: 10.18632/oncotarget.23761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 12/23/2017] [Indexed: 01/01/2023] Open
Abstract
In recent decades, emerging evidence demonstrates that ultraconserved elements (UCEs) encoding noncoding RNAs serve as regulators of gene expression. Until now, the role of uc.189 in human cancers remains undefined and the clinical significance of uc.189 in gynecological cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in gynecological cancers. Tissue microarrays were constructed with 243 samples including 116 cervical squamous cell carcinomas (CSCCs), 98 endometrial adenocarcinomas (EACs), 29 ovarian cystoadenocarcinomas(OCAs), and corresponding normal tissues. In CSCC, uc.189 expression was increased in 78.5% of cases (91/116), decreased in 4.3% (5/116), and unchanged in 17.2% (20/116). In EAC its expression was increased in 74.5% (73/98), decreased in 3.1% (3/98), and unchanged in 22.4% (22/98). Expression of uc.189 was increased in 23, and unchanged/decreased in 6, of 29 cases of ovarian cystoadenocarcinomas. Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in CSCC and EAC. Thus, these findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors.
Collapse
Affiliation(s)
- Lei Wang
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China.,Department of Pharmacy, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.,Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China
| | - Xing Cheng Wang
- Department of Pharmacy, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.,Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China
| | - Xinyu Li
- Department of Basic Medical, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.,Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China
| | - Yan Gu
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China
| | - Jun Zhou
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Shuwan Jiang
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Jiajia Liu
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Chong Wu
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Zhiyan Ding
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Yafeng Wan
- Department of Pharmacy, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.,Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China
| | - Chenghai Wang
- Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China.,Department of Pharmacy, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.,Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.,Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, China.,Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China
| |
Collapse
|
|
20
|
Long noncoding RNAs in the initiation, progression, and metastasis of hepatocellular carcinoma. Noncoding RNA Res 2017; 2:129-136. [PMID: 30159431 PMCID: PMC6084840 DOI: 10.1016/j.ncrna.2017.11.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/27/2017] [Accepted: 11/27/2017] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite awareness of risk factors for the development of HCC and advances in the diagnosis and clinical management of the disease, the molecular mechanisms underlying hepatocarcinogenesis remain poorly understood. Recent experimental studies provide strong evidence that long noncoding RNAs (lncRNAs), non-protein-coding transcripts with lengths >200 basepairs, contribute to the pathogenesis of numerous human diseases. Over the past decade, a role for lncRNAs in the initiation, progression, and metastasis of HCC has likewise emerged and developed into a highly active area of research. Although many lncRNAs appear to be dysregulated in HCC, extensive functional characterization has been performed on only a small proportion of these candidates to date. This review summarizes select lncRNAs that have been shown to wield functional relevance in the initiation, progression, or metastasis of HCC, focusing on the specific mechanisms by which lncRNA effects might be linked to clinical manifestations of the disease. In addition, an overview of circulating lncRNAs that have been identified as potential biomarkers for the diagnosis and prognosis of HCC is provided.
Collapse
|
|
21
|
Li H, Jiang L, Yu Z, Han S, Liu X, Li M, Zhu C, Qiao L, Huang L. The Role of a Novel Long Noncoding RNA TUC40- in Cardiomyocyte Induction and Maturation in P19 Cells. Am J Med Sci 2017; 354:608-616. [PMID: 29208259 DOI: 10.1016/j.amjms.2017.08.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 08/22/2017] [Accepted: 08/29/2017] [Indexed: 01/03/2023]
Abstract
BACKGROUND In previous studies, TUC40-, a new long noncoding RNA, was found to be overexpressed in human ventricular septal defect (VSD) embryonic heart samples. In this article, we carried out experiments on the P19 cell line to elucidate the effects of TUC40- overexpression on cardiomyocyte development relevant to VSD pathogenesis. METHODS We established the overexpression cell model by plasmid transfection, and explored the expression profile of Pbx1, the sense gene of TUC40-, and the marker genes of cardiomyocyte linage commitment (Nkx2.5 and GATA4) and maturation (cardiac troponin T). In addition, we combined cell cycle and Cell Counting Kit-8 analysis to detect cell proliferation and used flow cytometry and caspase-3 assays to test apoptosis. At last, bioinformatics analysis was performed to show the possible role of TUC40-. RESULTS In the control group, Pbx1 elevated steadily during cardiomyocyte induction; whereas in the overexpression group, it showed significantly lower expression at day 6, 8 and 10 of induction. Cells in the overexpression group failed to induce cardiomyocytes indicated by GATA4 and cardiac troponin T. Proliferation was inhibited possibly owing to G2/M cell cycle arrest and the induced apoptosis rate was higher in the overexpression group. CONCLUSIONS TUC40- overexpression reduced Pbx1 expression, cardiomyocyte induction and differentiation, inhibited proliferation and promoted apoptosis. Combining the results and previous studies, we propose TUC40- as a potential pathologic factor for VSD.
Collapse
Affiliation(s)
- Huijuan Li
- Department of Pediatrics, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu, China
| | - Li Jiang
- Department of Pediatrics, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu, China.
| | - Zhangbin Yu
- Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Shuping Han
- Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xuehua Liu
- Department of Cardiology, Nanjing Gulou Hospital, Nanjing, Jiangsu, China
| | - Mengmeng Li
- Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chun Zhu
- Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lixing Qiao
- Department of Pediatrics, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu, China
| | - Li Huang
- Department of Pediatrics, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu, China
| |
Collapse
|
|
22
|
Mehra M, Chauhan R. Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma. BIOMARKERS IN CANCER 2017; 9:1179299X17737301. [PMID: 29147078 PMCID: PMC5673005 DOI: 10.1177/1179299x17737301] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non-protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far.
Collapse
Affiliation(s)
- Mrigaya Mehra
- Studio of Computational Biology & Bioinformatics, Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, India
- Academy of Scientific & Innovative Research, Chennai, India
| | - Ranjit Chauhan
- Department of Hepatology, Loyola University Chicago, Chicago, IL, USA
- Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Health Sciences Center, Memorial University, St John’s, Newfoundland and Labrador, Canada
| |
Collapse
|
|
23
|
Huo X, Han S, Wu G, Latchoumanin O, Zhou G, Hebbard L, George J, Qiao L. Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: implications for tumorigenesis, disease progression, and liver cancer stem cells. Mol Cancer 2017; 16:165. [PMID: 29061150 PMCID: PMC5651571 DOI: 10.1186/s12943-017-0734-4] [Citation(s) in RCA: 143] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 10/16/2017] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with a poor prognosis worldwide. While early stage tumours can be treated with curative approaches such as liver transplantation or surgical resection, these are only suitable for a minority of patients. Those with advanced stage disease are only suitable for supportive approaches and most are resistant to the conventional chemotherapy or radiotherapy. Liver cancer stem cells (LCSCs) are a small subset of cancer cells with unlimited differentiation ability and tumour forming potential. In order to develop novel therapeutic approaches for HCC, we need to understand how the cancer develops and why treatment resistance occurs. Using high-throughput sequencing techniques, a large number of dysregulated long noncoding RNAs (lncRNAs) have been identified, and some of which are closely linked to key aspects of liver cancer pathology, progression, outcomes and for the maintenance of cancer stem cell-like properties. In addition, some lncRNAs are potential biomarkers for HCC diagnosis and may serve as the therapeutic targets. This review summarizes data recently reported lncRNAs that might be critical for the maintenance of the biological properties of LCSCs.
Collapse
Affiliation(s)
- Xiaoqi Huo
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia
| | - Shuanglin Han
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116027, China
| | - Guang Wu
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia
| | - Olivier Latchoumanin
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia
| | - Gang Zhou
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia
| | - Lionel Hebbard
- Department of Molecular and Cell Biology, Centre for Comparative Genomics, The Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Australian Institute of Tropical Health and Medicine, QLD, Townsville, 4811, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia
| | - Liang Qiao
- Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia.
| |
Collapse
|
|
24
|
Qiu L, Tang Q, Li G, Chen K. Long non-coding RNAs as biomarkers and therapeutic targets: Recent insights into hepatocellular carcinoma. Life Sci 2017; 191:273-282. [PMID: 28987633 DOI: 10.1016/j.lfs.2017.10.007] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/19/2017] [Accepted: 10/03/2017] [Indexed: 12/19/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer worldwide, and the survival rates of patients with HCC remains quite low after 5years. Long non-coding RNAs (LncRNAs) are a novel class of non-coding RNAs that are capable of regulating gene expression at various levels. Recent works have demonstrated that lncRNAs are often dysregulated in HCC, and the dysregulation of some of these lncRNAs are associated with the clinicopathological features of HCC. They regulate cell proliferation, apoptosis, autophagy, Epithelial-Mesenchymal Transition (EMT), invasion and metastasis of HCC by modulating gene expression and cancer-related signaling pathways, and thus contribute to the onset and progression of HCC. In this review, we provide a comprehensive survey of dysregulated lncRNAs in HCC, with particular focus on the functions and regulatory mechanisms of several essential and important lncRNAs, and discuss their potential clinical application as early diagnostic and/or prognostic biomarkers or therapeutic targets for HCC.
Collapse
Affiliation(s)
- Lipeng Qiu
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Qi Tang
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Guohui Li
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Keping Chen
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China.
| |
Collapse
|
|
25
|
Yao T, Chen Q, Fu L, Guo J. Circular RNAs: Biogenesis, properties, roles, and their relationships with liver diseases. Hepatol Res 2017; 47:497-504. [PMID: 28185365 DOI: 10.1111/hepr.12871] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 01/31/2017] [Accepted: 02/08/2017] [Indexed: 02/08/2023]
Abstract
Circular RNAs (circRNAs) are a class of new-found RNA molecules that have a special covalent loop structure without a 5' cap and 3' tail. Researchers have found that circRNAs may be generated by intron-pairing-driven or lariat-driven circularization. They are cleared up by way of extracellular vesicles. They have some advantages such as stability, conservation, and tissue specificity. By serving as sponges of microRNAs, interacting with long non-coding RNAs, mRNA, or proteins, circRNAs regulate gene expression at transcriptional and post-transcriptional levels and contribute to carcinogenesis. In recent years, circRNAs have been found to be correlated with many cancers including hepatocellular carcinoma, one of the most common cancers with high mortality. This article will first introduce the biogenesis, properties, and functions of circRNAs. Then we focus on the molecular mechanisms underlying some circRNAs, including hsa_circ_0001649, hsa_circ_0005075, and cerebellar degeneration-related protein 1 antisense, on hepatocellular carcinoma metastasis.
Collapse
Affiliation(s)
- Ting Yao
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Qingqing Chen
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Liyun Fu
- Ningbo No. 2 Hospital and the Affiliated Hospital, Medical School of Ningbo University, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| |
Collapse
|
|
26
|
Zhu X, Tian X, Yu C, Shen C, Yan T, Hong J, Wang Z, Fang JY, Chen H. A long non-coding RNA signature to improve prognosis prediction of gastric cancer. Mol Cancer 2016; 15:60. [PMID: 27647437 PMCID: PMC5029104 DOI: 10.1186/s12943-016-0544-0] [Citation(s) in RCA: 143] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 09/07/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Increasing evidence suggests long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, however, few related lncRNA signatures have been established for prediction of cancer prognosis. We aimed at developing alncRNA signature to improve prognosis prediction of gastric cancer (GC). METHODS Using a lncRNA-mining approach, we performed lncRNA expression profiling in large GC cohorts from Gene Expression Ominus (GEO), including GSE62254 data set (N = 300) and GSE15459 data set (N = 192). We established a set of 24-lncRNAs that were significantly associated with the disease free survival (DFS) in the test series. RESULTS Based on this 24-lncRNA signature, the test series patients could be classified into high-risk or low-risk subgroup with significantly different DFS (HR = 1.19, 95 % CI = 1.13-1.25, P < 0.0001). The prognostic value of this 24-lncRNA signature was confirmed in the internal validation series and another external validation series, respectively. Further analysis revealed that the prognostic value of this signature was independent of lymph node ratio (LNR) and postoperative chemotherapy. Gene set enrichment analysis (GSEA) indicated that high risk score group was associated with several cancer recurrence and metastasis associated pathways. CONCLUSIONS The identification of the prognostic lncRNAs indicates the potential roles of lncRNAs in GC biogenesis. Our results may provide an efficient classification tool for clinical prognosis evaluation of GC.
Collapse
Affiliation(s)
- Xiaoqiang Zhu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Xianglong Tian
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Chenyang Yu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Chaoqin Shen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Tingting Yan
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Jie Hong
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Zheng Wang
- Department of gastrointestinal surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| | - Haoyan Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001 China
| |
Collapse
|