|
1
|
Alimohammadi M, Fooladi AAI, Mafi A, Alavioun SM, Cho WC, Reiter RJ, Khormizi FZ, Yousefi T, Farahani N, Khoshnazar SM, Hushmandi K. Long noncoding RNAs and HPV-related cervical cancer: Uncovering molecular mechanisms and clinical applications. Transl Oncol 2025; 55:102363. [PMID: 40121995 PMCID: PMC11982485 DOI: 10.1016/j.tranon.2025.102363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 03/08/2025] [Accepted: 03/16/2025] [Indexed: 03/25/2025] Open
Abstract
Cervical cancer (CC) is the primary cause of cancer-related mortality among women in developing countries and is the most prevalent disease linked to human papillomavirus (HPV). Over 70 % of CC cases result from persistent infections with high-risk HPV types. The virus typically targets the mucocutaneous epithelium, generating viral particles in mature epithelial cells, which leads to disruptions in normal cell-cycle regulation and promotes uncontrolled cellular proliferation. This unchecked cell division results in the accumulation of genetic damage, contributing to the pathogenesis of CC. While HPV infection is a key etiological factor, the disease's progression also necessitates the involvement of genetic and epigenetic influences. One of the epigenetic regulators, long noncoding RNAs (lncRNAs), are characterized by transcripts exceeding 200 nucleotides. These molecules play crucial roles in various cellular processes, including transcription regulation, RNA metaboli35 per 100,000sm, and apoptosis. Investigating the specific roles of lncRNAs in modulating gene expression related to the oncogenic mechanisms of CC, particularly in the context of high-risk HPV infections, may provide valuable insights for diagnostic and therapeutic advancements. Herein, we first review key molecular mechanisms by which lncRNAs interfere with CC-related HPV development. Then, diagnostic, prognostic, and therapeutic potentials of these lncRNA molecules will be highlighted in depth. The focus of this article is on the role of lncRNAs associated with HPV-related CC, emphasizing the investigation of signaling pathways and their underlying molecular mechanisms. Furthermore, we explore the therapeutic potential and diagnostic relevance of the most significant lncRNAs in the context of CC, thereby highlighting their importance in advancing treatment strategies and improving patient outcomes.
Collapse
Affiliation(s)
- Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Ali Imani Fooladi
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Alireza Mafi
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Seyedeh Mana Alavioun
- Department of Basic sciences, Faculty of Veterinary Medicine, Urmia university, Urmia, Iran
| | - William C Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health San Antonio, Long School of Medicine, San Antonio, TX, USA
| | | | - Tooba Yousefi
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Seyedeh Mahdieh Khoshnazar
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
| | - Kiavash Hushmandi
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
2
|
Liao X, Yang L, Jiang M, Xin Y, Yan H, Qin Q, Chen M, Lu J. The Emerging Roles of Alternative Splicing in Human Oncovirus Infection. J Med Virol 2025; 97:e70346. [PMID: 40223738 DOI: 10.1002/jmv.70346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/07/2025] [Accepted: 04/01/2025] [Indexed: 04/15/2025]
Abstract
Alternative splicing (AS) is one of the most potent mechanisms for expanding the diversity of proteomes. During infection, human oncogenic viruses may exploit the AS to facilitate their replication cycle. Moreover, persistently infecting viruses can target key genes involved in classical signaling pathways to promote viral persistence and tumor progression. Here, we highlight how oncogenic viruses hijack AS system to manipulate host biological processes, and the host's AS system in turn modulates viral infection and replication. In addition, we have summarized the relatively underexplored involvement of noncoding RNAs in AS following tumor virus infection. This bidirectional interaction provides novel insights into interaction of virus-host and opens new avenues for therapeutic strategies targeting oncogenic viral infections.
Collapse
Affiliation(s)
- Xuefei Liao
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Li Yang
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Mingjuan Jiang
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Yujie Xin
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Huirong Yan
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Qingshuang Qin
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Mengdi Chen
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| | - Jianhong Lu
- Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
| |
Collapse
|
|
3
|
Hussain MS, Agrawal M, Shaikh NK, Saraswat N, Bahl G, Maqbool Bhat M, Khurana N, Bisht AS, Tufail M, Kumar R. Beyond the Genome: Deciphering the Role of MALAT1 in Breast Cancer Progression. Curr Genomics 2024; 25:343-357. [PMID: 39323624 PMCID: PMC11420562 DOI: 10.2174/0113892029305656240503045154] [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: 02/11/2024] [Revised: 03/25/2024] [Accepted: 04/04/2024] [Indexed: 09/27/2024] Open
Abstract
The MALAT1, a huge non-coding RNA, recently came to light as a multifaceted regulator in the intricate landscape of breast cancer (BC) progression. This review explores the multifaceted functions and molecular interactions of MALAT1, shedding light on its profound implications for understanding BC pathogenesis and advancing therapeutic strategies. The article commences by acknowledging the global impact of BC and the pressing need for insights into its molecular underpinnings. It is stated that the core lncRNA MALAT1 has a range of roles in both healthy and diseased cell functions. The core of this review unravels MALAT1's multifaceted role in BC progression, elucidating its participation in critical processes like resistance, invasion, relocation, and proliferating cells to therapy. It explores the intricate mechanisms through which MALAT1 modulates gene expression, interacts with other molecules, and influences signalling pathways. Furthermore, the paper emphasizes MALAT1's clinical significance as a possible prognostic and diagnostic biomarker. Concluding on a forward-looking note, the review highlights the broader implications of MALAT1 in BC biology, such as its connections to therapy resistance and metastasis. It underscores the significance of deeper investigations into these intricate molecular interactions to pave the way for precision medicine approaches. This review highlights the pivotal role of MALAT1 in BC progression by deciphering its multifaceted functions beyond the genome, offering profound insights into its implications for disease understanding and the potential for targeted therapeutic interventions.
Collapse
Affiliation(s)
- Md Sadique Hussain
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan (302017), India
| | - Mohit Agrawal
- Department of Pharmacology, School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram 122103, India
| | - Nusratbanu K. Shaikh
- Department of Quality Assurance, Smt. N. M. Padalia Pharmacy College, Ahmedabad, 382210, Gujarat, India
| | - Nikita Saraswat
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan (302017), India
| | - Gurusha Bahl
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan (302017), India
| | - Mudasir Maqbool Bhat
- Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, India
| | - Navneet Khurana
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Ajay Singh Bisht
- School of Pharmaceutical Sciences, Shri Guru Ram Rai University, Patel Nagar, Dehradun, Uttarakhand (248001), India
| | - Muhammad Tufail
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Rajesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| |
Collapse
|
|
4
|
Heidari-Ezzati S, Moeinian P, Ahmadian-Nejad B, Maghbbouli F, Abbasi S, Zahedi M, Afkhami H, Shadab A, Sajedi N. The role of long non-coding RNAs and circular RNAs in cervical cancer: modulating miRNA function. Front Cell Dev Biol 2024; 12:1308730. [PMID: 38434620 PMCID: PMC10906305 DOI: 10.3389/fcell.2024.1308730] [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: 10/09/2023] [Accepted: 01/24/2024] [Indexed: 03/05/2024] Open
Abstract
Cervical cancer (CC) is a primary global health concern, ranking as the fourth leading cause of cancer-related death in women. Despite advancements in prognosis, long-term outcomes remained poor. Beyond HPV, cofactors like dietary deficiencies, immunosuppression, hormonal contraceptives, co-infections, and genetic variations are involved in CC progression. The pathogenesis of various diseases, including cancer, has brought to light the critical regulatory roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). The aberrant expression of these miRNAs, lncRNAs, and circRNAs plays a pivotal role in the initiation and progression of CC. This review provides a comprehensive summary of the recent literature regarding the involvement of lncRNAs and circRNAs in modulating miRNA functions in cervical neoplasia and metastasis. Studies have shown that lncRNAs and circRNAs hold great potential as therapeutic agents and innovative biomarkers in CC. However, more clinical research is needed to advance our understanding of the therapeutic benefits of circRNAs and lncRNAs in CC.
Collapse
Affiliation(s)
- Sama Heidari-Ezzati
- School of Nursing and Midwifery, Bonab University of Medical Sciences, Bonab, Iran
| | - Parisa Moeinian
- Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Bahar Ahmadian-Nejad
- School of Nursing and Midwifery, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
| | | | - Sheida Abbasi
- Department of obstetrics and gynecology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahlagha Zahedi
- Department of Pathology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hamed Afkhami
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Alireza Shadab
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
- Iran University of Medical Sciences, Deputy of Health, Tehran, Iran
| | - Nayereh Sajedi
- Department of Anatomy, Faculty of Medicine, Qom Medical Sciences, Islamic Azad University, Qom, Iran
| |
Collapse
|
|
5
|
Rahni Z, Hosseini SM, Shahrokh S, Saeedi Niasar M, Shoraka S, Mirjalali H, Nazemalhosseini-Mojarad E, Rostami-Nejad M, Malekpour H, Zali MR, Mohebbi SR. Long non-coding RNAs ANRIL, THRIL, and NEAT1 as potential circulating biomarkers of SARS-CoV-2 infection and disease severity. Virus Res 2023; 336:199214. [PMID: 37657511 PMCID: PMC10502354 DOI: 10.1016/j.virusres.2023.199214] [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: 06/04/2023] [Revised: 08/23/2023] [Accepted: 08/29/2023] [Indexed: 09/03/2023]
Abstract
The current outbreak of coronavirus disease 2019 (COVID-19) is a global emergency, as its rapid spread and high mortality rate, which poses a significant threat to public health. Innate immunity plays a crucial role in the primary defense against infections, and recent studies have highlighted the pivotal regulatory function of long non-coding RNAs (lncRNAs) in innate immune responses. This study aims to assess the circulating levels of lncRNAs namely ANRIL, THRIL, NEAT1, and MALAT1 in the blood of moderate and severe SARS-CoV-2 infected patients, in comparison to healthy individuals. Additionally, it aims to explore the potential of these lncRNAs as biomarkers for determining the severity of the disease. The blood samples were collected from a total of 38 moderate and 25 severe COVID-19 patients, along with 30 healthy controls. The total RNA was extracted and qPCR was performed to evaluate the blood levels of the lncRNAs. The results indicate significantly higher expression levels of lncRNAs ANRIL and THRIL in severe patients when compared to moderate patients (P value = 0.0307, P value = 0.0059, respectively). Moreover, the expression levels of lncRNAs ANRIL and THRIL were significantly up-regulated in both moderate and severe patients in comparison to the control group (P value < 0.001, P value < 0.001, P value = 0.001, P value < 0.001, respectively). The expression levels of lncRNA NEAT1 were found to be significantly higher in both moderate and severe COVID-19 patients compared to the healthy group (P value < 0.001, P value < 0.001, respectively), and there was no significant difference in the expression levels of NEAT1 between moderate and severe patients (P value = 0.6979). The expression levels of MALAT1 in moderate and severe patients did not exhibit a significant difference compared to the control group (P value = 0.677, P value = 0.764, respectively). Furthermore, the discriminative power of ANRIL and THRIL was significantly higher in the severe patient group than the moderate group (Area under curve (AUC) = 0.6879; P-value = 0.0122, AUC = 0.6947; P-value = 0.0093, respectively). In conclusion, the expression levels of the lncRNAs ANRIL and THRIL are correlated with the severity of COVID-19 and can be regarded as circulating biomarkers for disease progression.
Collapse
Affiliation(s)
- Zeynab Rahni
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Seyed Masoud Hosseini
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Saeedi Niasar
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrzad Shoraka
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Habib Malekpour
- Research and Development Center, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
6
|
Zhu Y, Zhang F, Zhang S, Yi M. Predicting latent lncRNA and cancer metastatic event associations via variational graph auto-encoder. Methods 2023; 211:1-9. [PMID: 36709790 DOI: 10.1016/j.ymeth.2023.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/05/2022] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Long non-coding RNA (lncRNA) are shown to be closely associated with cancer metastatic events (CME, e.g., cancer cell invasion, intravasation, extravasation, proliferation) that collaboratively accelerate malignant cancer spread and cause high mortality rate in patients. Clinical trials may accurately uncover the relationships between lncRNAs and CMEs; however, it is time-consuming and expensive. With the accumulation of data, there is an urgent need to find efficient ways to identify these relationships. Herein, a graph embedding representation-based predictor (VGEA-LCME) for exploring latent lncRNA-CME associations is introduced. In VGEA-LCME, a heterogeneous combined network is constructed by integrating similarity and linkage matrix that can maintain internal and external characteristics of networks, and a variational graph auto-encoder serves as a feature generator to represent arbitrary lncRNA and CME pair. The final robustness predicted result is obtained by ensemble classifier strategy via cross-validation. Experimental comparisons and literature verification show better remarkable performance of VGEA-LCME, although the similarities between CMEs are challenging to calculate. In addition, VGEA-LCME can further identify organ-specific CMEs. To the best of our knowledge, this is the first computational attempt to discover the potential relationships between lncRNAs and CMEs. It may provide support and new insight for guiding experimental research of metastatic cancers. The source code and data are available at https://github.com/zhuyuan-cug/VGAE-LCME.
Collapse
Affiliation(s)
- Yuan Zhu
- School of Automation, China University of Geosciences, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China; Hubei Key Laboratory of Advanced Control and Intelligent Automation for Complex Systems, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China; Engineering Research Center of Intelligent Technology for Geo-Exploration, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China
| | - Feng Zhang
- School of Mathematics and Physics, China University of Geosciences, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China
| | - Shihua Zhang
- College of Life Science and Health, Wuhan University of Science and Technology, 974 Heping Avenue, Qingshan District, 430081, Wuhan, Hubei, China.
| | - Ming Yi
- School of Mathematics and Physics, China University of Geosciences, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China.
| |
Collapse
|
|
7
|
Hao L, Wu W, Xu Y, Chen Y, Meng C, Yun J, Wang X. LncRNA-MALAT1: A Key Participant in the Occurrence and Development of Cancer. Molecules 2023; 28:molecules28052126. [PMID: 36903369 PMCID: PMC10004581 DOI: 10.3390/molecules28052126] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/18/2023] [Accepted: 02/21/2023] [Indexed: 03/03/2023] Open
Abstract
LncRNAs are a group of non-coding RNA transcripts with lengths of over 200 nucleotides and can interact with DNA, RNA, and proteins to regulate gene expression of malignant tumors in human tissues. LncRNAs participate in vital processes, such as chromosomal nuclear transport in the cancerous site of human tissue, activation, and the regulation of proto-oncogenes, the differentiation of immune cells, and the regulation of the cellular immune system. The lncRNA metastasis-associated lung cancer transcript 1 (MALAT1) is reportedly involved in the occurrence and development of many cancers and serves as a biomarker and therapeutic target. These findings highlight its promising role in cancer treatment. In this article, we comprehensively summarized the structure and functions of lncRNA, notably the discoveries of lncRNA-MALAT1 in different cancers, the action mechanisms, and the ongoing research on new drug development. We believe our review would serve as a basis for further research on the pathological mechanism of lncRNA-MALAT1 in cancer and provide evidence and novel insights into its application in clinical diagnoses and treatments.
Collapse
Affiliation(s)
- Longhui Hao
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Wenzheng Wu
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Yankun Xu
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Yufan Chen
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Chengzhen Meng
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Jingyi Yun
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Xiaoyu Wang
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
- Correspondence:
| |
Collapse
|
|
8
|
Sabeena S. Role of noncoding RNAs with emphasis on long noncoding RNAs as cervical cancer biomarkers. J Med Virol 2023; 95:e28525. [PMID: 36702772 DOI: 10.1002/jmv.28525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/28/2022] [Accepted: 01/20/2023] [Indexed: 01/28/2023]
Abstract
Cervical cancer is a significant public health problem in developing countries, as most cases present at an advanced stage. This review aimed to analyze the role of noncoding RNAs as diagnostic and prognostic biomarkers in cervical cancers. Published studies on specific microRNA signatures in body fluids and cervical cancer tissues are highly heterogeneous, and there are no validated assays. The precision of the various immune-associated long noncoding (lncRNA) signatures should be assessed in clinical samples. Even though lncRNAs are tissue and cancer-specific, safe and appropriate methods for delivery to tumor tissues, toxicities and side effects are to be explored. Few studies have evaluated deregulated lncRNA expression levels with clinicopathological factors in a limited number of clinical samples. Prospective studies assessing the diagnostic and prognostic roles of circulating lncRNAs and P-Element-induced wimpy testis interacting PIWI RNAs (Piwil RNAs) in cervical cancer cases are essential. For the clinical application of lnc-RNA-based biomarkers, comprehensive research is needed as the impact of noncoding transcripts on molecular pathways is complex. The standardization and validation of deregulated ncRNAs in noninvasive samples of cervical cancer cases are needed.
Collapse
|
|
9
|
Reviewing the Potential Links between Viral Infections and TDP-43 Proteinopathies. Int J Mol Sci 2023; 24:ijms24021581. [PMID: 36675095 PMCID: PMC9867397 DOI: 10.3390/ijms24021581] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 01/15/2023] Open
Abstract
Transactive response DNA binding protein 43 kDa (TDP-43) was discovered in 2001 as a cellular factor capable to inhibit HIV-1 gene expression. Successively, it was brought to new life as the most prevalent RNA-binding protein involved in several neurological disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the fact that these two research areas could be considered very distant from each other, in recent years an increasing number of publications pointed out the existence of a potentially important connection. Indeed, the ability of TDP-43 to act as an important regulator of all aspects of RNA metabolism makes this protein also a critical factor during expression of viral RNAs. Here, we summarize all recent observations regarding the involvement of TDP-43 in viral entry, replication and latency in several viruses that include enteroviruses (EVs), Theiler's murine encephalomyelitis virus (TMEV), human immunodeficiency virus (HIV), human endogenous retroviruses (HERVs), hepatitis B virus (HBV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), West Nile virus (WNV), and herpes simplex virus-2 (HSV). In particular, in this work, we aimed to highlight the presence of similarities with the most commonly studied TDP-43 related neuronal dysfunctions.
Collapse
|
|
10
|
Wu S, Zhu H, Wu Y, Wang C, Duan X, Xu T. Molecular mechanisms of long noncoding RNAs associated with cervical cancer radiosensitivity. Front Genet 2023; 13:1093549. [PMID: 36685972 PMCID: PMC9846343 DOI: 10.3389/fgene.2022.1093549] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 12/16/2022] [Indexed: 01/06/2023] Open
Abstract
Despite advances in cervical cancer screening and human papilloma virus (HPV) vaccines, cervical cancer remains a global health burden. The standard treatment of cervical cancer includes surgery, radiation therapy, and chemotherapy. Radiotherapy (RT) is the primary treatment for advanced-stage disease. However, due to radioresistance, most patients in the advanced stage have an adverse outcome. Recent studies have shown that long noncoding RNAs (lncRNAs) participate in the regulation of cancer radiosensitivity by regulating DNA damage repair, apoptosis, cancer stem cells (CSCs), and epithelial-mesenchymal transition (EMT). In this review, we summarize the molecular mechanisms of long noncoding RNAs in cervical cancer and radiosensitivity, hoping to provide a theoretical basis and a new molecular target for the cervical cancer RT in the clinic.
Collapse
Affiliation(s)
| | | | | | | | | | - Tianmin Xu
- Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
11
|
Functional roles of long noncoding RNA MALAT1 in gynecologic cancers. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023; 25:48-65. [PMID: 36042115 DOI: 10.1007/s12094-022-02914-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023]
Abstract
Gynecologic cancers are reproductive disorders characterized by pelvic pain and infertility. The identification of new predictive markers and therapeutic targets for the treatment of gynecologic cancers is urgently necessary. One of the recent successes in gynecologic cancers research is identifying the role of signaling pathways in the pathogenesis of the disease. Recent experiments showed long noncoding RNAs (lncRNA) can be novel therapeutic approaches for the diagnosis and treatment of gynecologic cancers. LncRNA are transcribed RNA molecules that play pivotal roles in multiple biological processes by regulating the different steps of gene expression. Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) is a well-known lncRNA that plays functional roles in gene expression, RNA processing, and epigenetic regulation. High expression of MALAT1 is closely related to numerous human diseases. It is generally believed that MALAT1 expression is associated with cancer cell growth, autophagy, invasion, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) could contribute to the pathogenesis of gynecologic cancers. In this review, we will summarize functional roles of MALAT1 in the most common gynecologic cancers, including endometrium, breast, ovary, and cervix.
Collapse
|
|
12
|
Network analysis of long non-coding RNA expression profiles in common warts. Heliyon 2022; 8:e11790. [DOI: 10.1016/j.heliyon.2022.e11790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 04/15/2022] [Accepted: 11/14/2022] [Indexed: 11/20/2022] Open
|
|
13
|
Shetty A, Venkatesh T, Kabbekodu SP, Tsutsumi R, Suresh PS. LncRNA-miRNA-mRNA regulatory axes in endometrial cancer: a comprehensive overview. Arch Gynecol Obstet 2022; 306:1431-1447. [PMID: 35182183 DOI: 10.1007/s00404-022-06423-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Recent research on tumorigenesis and progression has opened up an array of novel molecular mechanisms in the form of interactions between cellular non-coding RNAs (long non-coding RNA[lncRNA]/microRNA [miRNA]) and coding transcripts that regulate health and disease. Endometrial cancer (EC) is a prominent gynecological malignancy with a high incidence rate and poorly known etiology and prognostic factors that hinder the success of disease management. The emerging role of lncRNA-miRNA-mRNA interactions and their dysregulation in the pathophysiology of EC has been elucidated in many recent studies. METHODS A thorough literature review was conducted to explore information about lncRNA-miRNA-mRNA axes in EC. RESULTS Several lncRNAs act as molecular sponges that sequester various tumor suppressor miRNAs to inhibit their function, leading to the dysregulation of their target mRNA transcripts that contribute to the EC regulation. CONCLUSIONS This review summarizes these networks of molecular mechanisms and their contribution to different aspects of endometrial carcinogenesis, leading to a better conceptualization of the molecular pathways that underlie the disease and helping establish novel diagnostic biomarkers and therapeutic intervention points to aid the curative intent of EC.
Collapse
Affiliation(s)
- Abhishek Shetty
- Department of Biosciences, Mangalore University, Mangalagangothri, Mangalore, 574 199, Karnataka, India
| | - Thejaswini Venkatesh
- Department of Biochemistry and Molecular Biology, Central University of Kerala, Kasargod, 671316, Kerala, India
| | - Shama Prasada Kabbekodu
- Department of Cell and Molecular Biology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Rie Tsutsumi
- Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, 770-8503, Japan
| | - Padmanaban S Suresh
- School of Biotechnology, National Institute of Technology, Calicut, 673601, Kerala, India.
| |
Collapse
|
|
14
|
Basera A, Hull R, Demetriou D, Bates DO, Kaufmann AM, Dlamini Z, Marima R. Competing Endogenous RNA (ceRNA) Networks and Splicing Switches in Cervical Cancer: HPV Oncogenesis, Clinical Significance and Therapeutic Opportunities. Microorganisms 2022; 10:1852. [PMID: 36144454 PMCID: PMC9501168 DOI: 10.3390/microorganisms10091852] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/25/2022] [Accepted: 09/09/2022] [Indexed: 12/20/2022] Open
Abstract
Cervical cancer (CC) is the primary cause of female cancer fatalities in low-middle-income countries (LMICs). Persistent infections from the human papillomavirus (HPV) can result in cervical cancer. However, numerous different factors influence the development and progression of cervical cancer. Transcriptomic knowledge of the mechanisms with which HPV causes cervical cancer pathogenesis is growing. Nonetheless, there is an existing gap hindering the development of therapeutic approaches and the improvement of patient outcomes. Alternative splicing allows for the production of numerous RNA transcripts and protein isoforms from a single gene, increasing the transcriptome and protein diversity in eukaryotes. Cancer cells exhibit astounding transcriptome modifications by expressing cancer-specific splicing isoforms. High-risk HPV uses cellular alternative splicing events to produce viral and host splice variants and proteins that drive cancer progression or contribute to distinct cancer hallmarks. Understanding how viruses utilize alternative splicing to drive pathogenesis and tumorigenesis is essential. Although research into the role of miRNAs in tumorigenesis is advancing, the function of other non-coding RNAs, including lncRNA and circRNA, has been understudied. Through their interaction with mRNA, non-coding RNAs form a network of competing endogenous RNAs (ceRNAs), which regulate gene expression and promote cervical cancer development and advancement. The dysregulated expression of non-coding RNAs is an understudied and tangled process that promotes cervical cancer development. This review will present the role of aberrant alternative splicing and immunosuppression events in HPV-mediated cervical tumorigenesis, and ceRNA network regulation in cervical cancer pathogenesis will also be discussed. Furthermore, the therapeutic potential of splicing disruptor drugs in cervical cancer will be deliberated.
Collapse
Affiliation(s)
- Afra Basera
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
- Department of Medical Oncology, Steve Biko Academic Hospital and University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Rodney Hull
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Demetra Demetriou
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - David Owen Bates
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
- David Owen Bates, Division of Cancer and Stem Cells, Centre for Cancer Sciences, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK
| | - Andreas Martin Kaufmann
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
- Clinic for Gynaecology, Laboratory for Gynaecologic Tumor Immunology, Institute of Health, Charité-Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Augustenburgerplatz 1, 13353 Berlin, Germany
| | - Zodwa Dlamini
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Rahaba Marima
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa
| |
Collapse
|
|
15
|
The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9. JOURNAL OF ONCOLOGY 2022; 2022:3448224. [PMID: 35979035 PMCID: PMC9377974 DOI: 10.1155/2022/3448224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/17/2022] [Indexed: 11/18/2022]
Abstract
Objective. The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women’s health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the role of lncRNA SCIRT in the development of CC. Methods. The expression profile of long noncoding RNA stem cell inhibitory RNA transcript (lncRNA SCIRT) in CC (n = 34), tumor-adjacent tissue, and CC cell culture was determined through fluorescence quantitative PCR. The knockdown /overexpressed lncRNA SCIRT vectors were constructed and transfected into cells, and the effects of knockdown or overexpression of lncRNA SCIRT on the proliferative, invasive, and migratory properties of CC cells were determined through Cell Counting Kit-8 (CCK-8), colony forming, and Transwell experiments. Western blot was employed to determine the knockdown/overexpression efficiency of SCIRT and its role on the expression of proteins (e-cadherin, n-cadherin, vimentin, matrix metalloproteinase (MMP)-9 and MMP-2) in CC cells. Finally, SCIRT knockdown on the proliferative ability for CC cells was determined through tumorigenic experiment in nude mice. Results. LncRNA SCIRT was highly expressed in CC tissues and cells, and significantly linked with clinical/pathology-based characteristics of patients, including Federation Internationale of Gynecologie and Obstetrigue (FIGO) stage, tumor dimensions, and lymph-node metastasis. SCIRT knockdown markedly reduced CC proliferative, colony forming, and invasive properties, while overexpressing SCIRT promoted the proliferative and invasive properties of CC. Western blotting analysis demonstrated that SCIRT knockdown upregulated e-cadherin and downregulated n-cadherin, vimentin, MMP-9, and MMP-2. Meanwhile, overexpressing SCIRT of lncRNA SCIRT had the opposite effect. Tumorigenic experiment showed that SCIRT knockdown could markedly reduce CC proliferative property the nude mouse. Conclusion. LncRNA SCIRT was highly expressed in CC clinical cases. Knockdown/overexpressing SCIRT affected CC proliferative/invasive properties. Hence, lncRNA SCIRT is a promising drug-target and a new biological diagnostic molecule for CC patients.
Collapse
|
|
16
|
Parashar D, Singh A, Gupta S, Sharma A, Sharma MK, Roy KK, Chauhan SC, Kashyap VK. Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer. Genes (Basel) 2022; 13:genes13071254. [PMID: 35886037 PMCID: PMC9317009 DOI: 10.3390/genes13071254] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 12/06/2022] Open
Abstract
Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome's composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR-Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC.
Collapse
Affiliation(s)
- Deepak Parashar
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, MI 53226, USA
- Correspondence: (D.P.); (V.K.K.); Tel.: +1-414-439-8089 (D.P.); +1-956-296-1738 (V.K.K.)
| | - Anupam Singh
- Department of Biotechnology, GLA University, Mathura 281406, Uttar Pradesh, India; (A.S.); (S.G.)
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura 281406, Uttar Pradesh, India; (A.S.); (S.G.)
| | - Aishwarya Sharma
- Sri Siddhartha Medical College and Research Center, Tumkur 572107, Karnataka, India;
| | - Manish K. Sharma
- Department of Biotechnology, IP College, Bulandshahr 203001, Uttar Pradesh, India;
| | - Kuldeep K. Roy
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun 248007, Uttarakhand, India;
| | - Subhash C. Chauhan
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Vivek K. Kashyap
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Correspondence: (D.P.); (V.K.K.); Tel.: +1-414-439-8089 (D.P.); +1-956-296-1738 (V.K.K.)
| |
Collapse
|
|
17
|
Pi L, Yang L, Fang BR, Meng XX, Qian L. LncRNA MALAT1 from human adipose-derived stem cell exosomes accelerates wound healing via miR-378a/FGF2 axis. Regen Med 2022; 17:627-641. [PMID: 35822640 DOI: 10.2217/rme-2021-0170] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: The effects of MALAT1 from human adipose-derived stem cell (ADSC) exosomes in skin wound healing were investigated. Material & methods: The viability, apoptosis and migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometry and scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosis and inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2 expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.
Collapse
Affiliation(s)
- Li Pi
- Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China
| | - Li Yang
- Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China
| | - Bai-Rong Fang
- Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China
| | - Xian-Xi Meng
- Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China
| | - Li Qian
- Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China
| |
Collapse
|
|
18
|
Makgoo L, Mosebi S, Mbita Z. Long noncoding RNAs (lncRNAs) in HIV-mediated carcinogenesis: Role in cell homeostasis, cell survival processes and drug resistance. Noncoding RNA Res 2022; 7:184-196. [PMID: 35991514 PMCID: PMC9361211 DOI: 10.1016/j.ncrna.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 07/04/2022] [Accepted: 07/20/2022] [Indexed: 12/24/2022] Open
Abstract
There is accruing data implicating long non-coding RNAs (lncRNAs) in the development and progression of non-communicable diseases such as cancer. These lncRNAs have been implicated in many diverse HIV-host interactions, some of which are beneficial to HIV propagation. The virus-host interactions induce the expression of HIV-regulated long non-coding RNAs, which are implicated in the carcinogenesis process, therefore, it is critical to understand the molecular mechanisms that underpin these HIV-regulated lncRNAs, especially in cancer formation. Herein, we summarize the role of HIV-regulated lncRNAs targeting cancer development-related processes including apoptosis, cell cycle, cell survival signalling, angiogenesis and drug resistance. It is unclear how lncRNAs regulate cancer development, this review also discuss recent discoveries regarding the functions of lncRNAs in cancer biology. Innovative research in this field will be beneficial for the future development of therapeutic strategies targeting long non-coding RNAs that are regulated by HIV, especially in HIV associated cancers.
Collapse
|
|
19
|
Guan HM, Li WQ, Liu J, Zhou JY. LncRNA HIF1A-AS2 modulated by HPV16 E6 regulates apoptosis of cervical cancer cells via P53/caspase9/caspase3 axis. Cell Signal 2022; 97:110390. [PMID: 35728704 DOI: 10.1016/j.cellsig.2022.110390] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Plentiful evidence proves that lncRNAs play a crucial role in tumor development. However, the function and mechanism that were mediated by lncRNA HIF1A-AS2 in cervical cancer remain unclear. METHODS The lncRNA HIF1A-AS2 was identified via high-throughput microarray analysis of three HPV 16-positive cervical squamous cell carcinoma (CSCC) samples and three HPV-negative normal controls. The expression of HIF1A-AS2 was detected by qRT-PCR in clinical tissues and cancer cells. In vitro and in vivo assays were performed through downregulation or upregulation of HIF1A-AS2. The possible mechanisms of HIF1A-AS2 in cervical cancer cells were explored by western blot, flow cytometric analysis and rescue assays. RESULTS HIF1A-AS2 was significantly increased in cervical cancer tissue, and in the HPV- positive cervical cancer cells. Further investigation showed that the inhibition of HIF1A-AS2 suppressed cell proliferation, migration, invasion, and induced apoptosis, while up-regulation of HIF1A-AS2 revealed opposite results. In terms of mechanism, we found that HIF1A-AS2 was mediated by HPV16 E6 and regulated cell apoptosis via P53/caspase 9/caspase 3 axis. CONCLUSION Our findings demonstrate that HIF1A-AS2 functions as a carcinogenic lncRNA that promotes tumor development, and serves as a candidate prognostic factor, which may contribute to the treatment of cervical cancer.
Collapse
Affiliation(s)
- Hong-Mei Guan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Wen-Qi Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Jie Liu
- Department of Gynaecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Jue-Yu Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
| |
Collapse
|
|
20
|
Hu XL, Huang XT, Zhang JN, Liu J, Wen LJ, Xu X, Zhou JY. Long noncoding RNA MIR210HG is induced by hypoxia-inducible factor 1α and promotes cervical cancer progression. Am J Cancer Res 2022; 12:2783-2797. [PMID: 35812055 PMCID: PMC9251695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 05/28/2022] [Indexed: 06/15/2023] Open
Abstract
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other's expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.
Collapse
Affiliation(s)
- Xiao-Lin Hu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| | - Xia-Tong Huang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
- The First School of Clinical Medicine, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| | - Jia-Ni Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
- The First School of Clinical Medicine, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| | - Jie Liu
- Department of Gynaecology and Obstetrics, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| | - Li-Jun Wen
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
- School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| | - Xin Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| | - Jue-Yu Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China
| |
Collapse
|
|
21
|
Garrido MP, Fredes AN, Lobos-González L, Valenzuela-Valderrama M, Vera DB, Romero C. Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer. Biomedicines 2021; 10:77. [PMID: 35052757 PMCID: PMC8772950 DOI: 10.3390/biomedicines10010077] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 12/17/2022] Open
Abstract
Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies. The late diagnosis is frequent due to the absence of specific symptomatology and the molecular complexity of the disease, which includes a high angiogenesis potential. The first-line treatment is based on optimal debulking surgery following chemotherapy with platinum/gemcitabine and taxane compounds. During the last years, anti-angiogenic therapy and poly adenosine diphosphate-ribose polymerases (PARP)-inhibitors were introduced in therapeutic schemes. Several studies have shown that these drugs increase the progression-free survival and overall survival of patients with ovarian cancer, but the identification of patients who have the greatest benefits is still under investigation. In the present review, we discuss about the molecular characteristics of the disease, the recent evidence of approved treatments and the new possible complementary approaches, focusing on drug repurposing, non-coding RNAs, and nanomedicine as a new method for drug delivery.
Collapse
Affiliation(s)
- Maritza P. Garrido
- Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile; (A.N.F.); (D.B.V.)
- Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
| | - Allison N. Fredes
- Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile; (A.N.F.); (D.B.V.)
| | - Lorena Lobos-González
- Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile;
| | - Manuel Valenzuela-Valderrama
- Laboratorio de Microbiología Celular, Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8320000, Chile;
| | - Daniela B. Vera
- Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile; (A.N.F.); (D.B.V.)
| | - Carmen Romero
- Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile; (A.N.F.); (D.B.V.)
- Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
| |
Collapse
|
|
22
|
Molecular Markers to Predict Prognosis and Treatment Response in Uterine Cervical Cancer. Cancers (Basel) 2021; 13:cancers13225748. [PMID: 34830902 PMCID: PMC8616420 DOI: 10.3390/cancers13225748] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/12/2021] [Accepted: 11/14/2021] [Indexed: 02/07/2023] Open
Abstract
Uterine cervical cancer is one of the leading causes of cancer-related mortality in women worldwide. Each year, over half a million new cases are estimated, resulting in more than 300,000 deaths. While less-invasive, fertility-preserving surgical procedures can be offered to women in early stages, treatment for locally advanced disease may include radical hysterectomy, primary chemoradiotherapy (CRT) or a combination of these modalities. Concurrent platinum-based chemoradiotherapy regimens remain the first-line treatments for locally advanced cervical cancer. Despite achievements such as the introduction of angiogenesis inhibitors, and more recently immunotherapies, the overall survival of women with persistent, recurrent or metastatic disease has not been extended significantly in the last decades. Furthermore, a broad spectrum of molecular markers to predict therapy response and survival and to identify patients with high- and low-risk constellations is missing. Implementation of these markers, however, may help to further improve treatment and to develop new targeted therapies. This review aims to provide comprehensive insights into the complex mechanisms of cervical cancer pathogenesis within the context of molecular markers for predicting treatment response and prognosis.
Collapse
|
|
23
|
Wang T, Zhang W, Huang W, Hua Z, Li S. LncRNA MALAT1 was regulated by HPV16 E7 independently of pRB in cervical cancer cells. J Cancer 2021; 12:6344-6355. [PMID: 34659524 PMCID: PMC8489136 DOI: 10.7150/jca.61194] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 08/21/2021] [Indexed: 12/26/2022] Open
Abstract
High-risk human papillomavirus (HPV) infection was one of the first step in the process of carcinogenesis in cervical cancers. The expression of viral oncoprotein E7 was essential in this process by inactivating the tumor suppressor proteins RB, in addition to interacting with other host proteins. LncRNA MALAT1 was found to be altered in human cervical cancer tissues, suggesting an important role in tumorigenesis. Moreover, MALAT1 was also overexpressed in HPV16 positive cervical cancer cell lines in an HPV16 E7 dependent manner. To explore the mechanism of E7 involved in MALAT1 up-regulation, the deletion mutant E7∆N and E7∆C were constructed to test the functional domain of E7 for MALAT1 regulation. ChIP, EMSA and UV crosslink were performed to detect the interaction between E7 and MALAT1 promoter. E7 and E7∆N mutant were observed that could bind with MALAT1 promoter directly and interacted with SP1 to form triple complex. E7-SP1 interaction contributed to the transcription activation of MALAT1 promoter. E7 and E7∆N also could promote cell proliferation, invasion, and migration, and the stimulating effect could be reversed by siMALAT1. Here we showed that HPV16 E7 as well as E7∆N could associate with SP1 and bound directly to MALAT1 promoter in vitro and in vivo. This function way of E7 was independent of pRB in cervical cancer cells. To our knowledge, this was the first reported function model for E7 as transcription activator to directly bind to the target promoter.
Collapse
Affiliation(s)
- Ting Wang
- Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China
| | - Wei Zhang
- Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China
| | - Wenbin Huang
- Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Zichun Hua
- The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210046.,Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, Jiangsu 213164, P.R. China
| | - Shufeng Li
- Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China
| |
Collapse
|
|
24
|
Lamsisi M, Wakrim L, Bouziyane A, Benhessou M, Oudghiri M, Laraqui A, Elkarroumi M, Ennachit M, El Mzibri M, Ennaji MM. The Biological Significance of Long noncoding RNAs Dysregulation and their Mechanism of Regulating Signaling Pathways in Cervical Cancer. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2021; 10:75-101. [PMID: 34703793 PMCID: PMC8496250 DOI: 10.22088/ijmcm.bums.10.2.75] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 08/01/2021] [Indexed: 12/19/2022]
Abstract
Despite the remarkable decrease in cervical cancer incidence due to the availability of the HPV vaccine and implementation of screening programs for early detection in developed countries, this cancer remains a major health problem globally, especially in developing countries where most of the cases and mortality occur. Therefore, more understanding of molecular mechanisms of cervical cancer development might lead to the discovery of more effective diagnosis and treatment options. Research on long noncoding RNAs (lncRNAs) demonstrates the important roles of these molecules in many physiological processes and diseases, especially cancer. In the present review, we discussed the significance of lncRNAs altered expression in cervical cancer, highlighting their roles in regulating highly conserved signaling pathways, such as mitogen-activated protein kinase (MAPK), Wnt/β-catenin, Notch, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways and their association with the progression of cervical cancer in order to bring more insight and understanding of this disease and their potential implications in cancer diagnosis and therapy.
Collapse
Affiliation(s)
- Maryame Lamsisi
- Team of Virology, Oncology and Medical Biotechnologies, Laboratory of Virology, Microbiology, Quality, and Biotechnologies/ ETB. Faculty of Science and Techniques Mohammedia, Hassan II University of Casablanca, Morocco.
| | - Lahcen Wakrim
- Laboratory of Virology, Pasteur Institute of Morocco. Casablanca, Morocco.
| | - Amal Bouziyane
- Team of Virology, Oncology and Medical Biotechnologies, Laboratory of Virology, Microbiology, Quality, and Biotechnologies/ ETB. Faculty of Science and Techniques Mohammedia, Hassan II University of Casablanca, Morocco.
- University Mohammed VI of Health Science, Casablanca, Morocco.
| | - Mustapha Benhessou
- Team of Virology, Oncology and Medical Biotechnologies, Laboratory of Virology, Microbiology, Quality, and Biotechnologies/ ETB. Faculty of Science and Techniques Mohammedia, Hassan II University of Casablanca, Morocco.
- School of Medicine and Pharmacy, University Hassan II of Casablanca, Morocco.
| | - Mounia Oudghiri
- Immunology and Biodiversity laboratory, Faculty of Sciences Ain chock, Hassan II University of Casablanca, Morocco.
| | - Abdelilah Laraqui
- Research and Biosafety Laboratory, Mohammed V Military Hospital, University Mohammed V of Rabat, Morocco.
| | - Mohamed Elkarroumi
- School of Medicine and Pharmacy, University Hassan II of Casablanca, Morocco.
| | - Mohammed Ennachit
- School of Medicine and Pharmacy, University Hassan II of Casablanca, Morocco.
| | | | - Moulay Mustapha Ennaji
- Corresponding author: Faculty of Science and Techniques Mohammedia, University Hassan II of Casablanca, Morocco. E-mail:
| |
Collapse
|
|
25
|
Liu Y, Tu H, Zhang L, Xiong J, Li L. FOXP3‑induced LINC00885 promotes the proliferation and invasion of cervical cancer cells. Mol Med Rep 2021; 23:458. [PMID: 33880574 PMCID: PMC8072316 DOI: 10.3892/mmr.2021.12097] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 01/07/2021] [Indexed: 01/29/2023] Open
Abstract
Cervical cancer (CC) is the fourth most common type of cancer in women worldwide. LINC00885, a novel oncogenic type of long non-coding RNA, is upregulated in various types of cancer, but its expression in CC remains unknown. The aim of the present study was to investigate the expression of LINC00885 in CC, and its effect on the proliferation and invasion of CC cells in vitro. The expression levels of LINC00885 and forkhead box protein 3 (FOXP3) from The Cancer Genome Atlas (TCGA) were selected to analyze the differences between CC tissues and normal cervical tissues using bioinformatics analyses. Reverse transcription-quantitative (RT-q)PCR was used to detect the relative expression of LINC00885 in CC cell lines, and its expression was knocked down. Cell Counting Kit-8 assays and EdU staining were used to detect the changes in cell proliferative capacity of cells. Transwell experiments were used to examine cell invasion. Dual-luciferase reporter and chromatin immunoprecipitation assays were performed to examine the interactions between LINC00885 and FOXP3. FOXP3 and epithelial-mesenchymal transition (EMT)-related proteins were detected using western blotting. The expression of LINC00885 and FOXP3 in CC tissues and CC cells was significantly higher compared with the normal cervical tissues and normal cervical epithelial cells. FOXP3 could specifically interact with the promoter of LINC00885 and activate LINC00885 transcription. Knockdown of LINC00885 and silencing of FOXP3 significantly inhibited proliferation, invasion and EMT of CC cells. Overexpression of LINC00885 reversed the inhibitory effects of FOXP3 knockdown on the proliferation and invasion of CC cells. Collectively, LINC00885 and FOXP3 may serve as biomarkers for the early diagnosis of CC and as a potential therapeutic target for reversing the malignant phenotype of CC.
Collapse
Affiliation(s)
- Yawen Liu
- Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Haiyan Tu
- Department of Gynecological Oncology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China
| | - Lingling Zhang
- Department of Gynecological Oncology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China
| | - Jianping Xiong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Ling Li
- Department of Gynecological Oncology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China
| |
Collapse
|
|
26
|
Dias TR, Santos JMO, Gil da Costa RM, Medeiros R. Long non-coding RNAs regulate the hallmarks of cancer in HPV-induced malignancies. Crit Rev Oncol Hematol 2021; 161:103310. [PMID: 33781867 DOI: 10.1016/j.critrevonc.2021.103310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 03/22/2021] [Accepted: 03/23/2021] [Indexed: 02/07/2023] Open
Abstract
High-risk human papillomavirus (HPV) is the most frequent sexually transmitted agent worldwide and is responsible for approximately 5% of human cancers. Identifying novel biomarkers and therapeutic targets for these malignancies requires a deeper understanding of the mechanisms involved in the progression of HPV-induced cancers. Long non-coding RNAs (lncRNAs) are crucial in the regulation of biological processes. Importantly, these molecules are key players in the progression of multiple malignancies and are able to regulate the development of the different hallmarks of cancer. This review highlights the action of lncRNAs in the regulation of cellular processes leading to the typical hallmarks of cancer. The regulation of lncRNAs by HPV oncogenes, their targets and also their mechanisms of action are also discussed, in the context of HPV-induced malignancies. Overall, accumulating data indicates that lncRNAs may have a significant potential to become useful tools for clinical practice as disease biomarkers or therapy targets.
Collapse
Affiliation(s)
- Tânia R Dias
- Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal; Faculty of Medicine of the University of Porto (FMUP), 4200-319, Porto, Portugal; Research Department of the Portuguese League Against Cancer-Regional Nucleus of the North (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte), 4200-177, Porto, Portugal.
| | - Joana M O Santos
- Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal; Faculty of Medicine of the University of Porto (FMUP), 4200-319, Porto, Portugal.
| | - Rui M Gil da Costa
- Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal; LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465, Porto, Portugal; Postgraduate Programme in Adult Health (PPGSAD), Tumour and DNA Biobank, Federal University of Maranhão (UFMA), 65080-805, São Luís, Brazil.
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal; Faculty of Medicine of the University of Porto (FMUP), 4200-319, Porto, Portugal; Research Department of the Portuguese League Against Cancer-Regional Nucleus of the North (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte), 4200-177, Porto, Portugal; Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072, Porto, Portugal; CEBIMED, Faculty of Health Sciences of the Fernando Pessoa University, 4249-004, Porto, Portugal.
| |
Collapse
|
|
27
|
Scarth JA, Patterson MR, Morgan EL, Macdonald A. The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation. J Gen Virol 2021; 102:001540. [PMID: 33427604 PMCID: PMC8148304 DOI: 10.1099/jgv.0.001540] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 11/25/2020] [Indexed: 12/24/2022] Open
Abstract
Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.
Collapse
Affiliation(s)
- James A. Scarth
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
- Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
| | - Molly R. Patterson
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
- Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
| | - Ethan L. Morgan
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
- Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
- Present address: Tumour Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institute of Health, Bethesda, MD 20892, USA
| | - Andrew Macdonald
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
- Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK
| |
Collapse
|
|
28
|
Qiao FH, Tu M, Liu HY. Role of MALAT1 in gynecological cancers: Pathologic and therapeutic aspects. Oncol Lett 2021; 21:333. [PMID: 33692865 DOI: 10.3892/ol.2021.12594] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 02/02/2021] [Indexed: 12/15/2022] Open
Abstract
Gynecological cancers, including breast, ovarian, uterine, vaginal, cervical and vulvar cancers are among the major threats to modern life, particularly to female health. Long non-coding RNAs (lncRNAs) play critical roles in normal development of organisms, as well as the tumorigenesis process, and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a large infrequently spliced lncRNA, which have been implicated in different gynecological cancers. MALAT1 is overexpressed in breast, ovarian, cervical and endometrial cancers, which initiates cancer progression by inducing changes in the expression of several anti-apoptotic and epithelial-to-mesenchymal transition-related genes. Targeting MALAT1 is an important strategy to combat gynecological cancers, and application of RNA-interference technology and chemotherapeutic process are crucial to target and minimize MALAT1 activity. The present review discusses the role of MALAT1 in gynecological cancers, and potential strategies to target this lncRNA to develop cancer therapeutics. However, further clinical studies are required to determine the prognostic potential of MALAT1 in gynecological cancers.
Collapse
Affiliation(s)
- Feng-Hua Qiao
- Department of Gynecology, Second People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China
| | - Min Tu
- Department of Orthopedics, Second People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China
| | - Hong-Yan Liu
- Department of Gynecology, Maternal and Child Health Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China
| |
Collapse
|
|
29
|
Ray SK, Mukherjee S. LncRNAs as Architects in Cancer Biomarkers with Interface of Epitranscriptomics- Incipient Targets in Cancer Therapy. Curr Cancer Drug Targets 2021; 21:416-427. [PMID: 33413062 DOI: 10.2174/1568009620666210106122421] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/22/2020] [Accepted: 11/23/2020] [Indexed: 11/22/2022]
Abstract
Long non-coding RNAs (LncRNAs) epitomize a class of non-coding regulatory RNAs with more than 200 nucleotides, which are long and situated in the nucleus or cytoplasm and rarely encode proteins. Accruing evidence signposts that lncRNAs act as molecular switches in different cellular activities like differentiation, apoptosis, as well as reprogramming of cellular states by modifying gene expression patterns. The revelation of immense numbers of lncRNA with their wide variety of expression patterns in different kinds of malignancy, tumor explicitness, and their steadiness in circulating body fluids deliver an innovative groundwork for emerging diagnosis and treatments for cancer. Mechanisms associating lncRNAs in carcinogenesis are conquered by deregulation of cellular signaling pathways and altered epitranscriptome along with their expression. Specified these attributes, it becomes clear that the improvement of new tools to identify lncRNAs with higher affectability will be fundamental to allow the identification of the expression pattern of lncRNAs in various kinds of malignant growth and may likewise be utilized to envisage cancer prognosis in addition to the patients' outcome. Improvement of RNA targeting-based therapeutics is delivering incredible prospects to modulate lncRNAs for anti-cancer initiatives. Henceforth, lncRNAs can be used exclusively as possible cancer biomarkers for early diagnosis and anticipation of malignancy, as well as metastasis. In addition to the basic curative targets and along these, lncRNAs hold resilient assurance towards the revelation of innovative diagnostics and therapeutics for malignant growth with the interface of epitranscriptomics information. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis, regulation, and lncRNA-associated epigenetics of cancer along with targeting lncRNAs with potential approaches for impending diagnosis and therapeutic intervention in malignancies.
Collapse
Affiliation(s)
- Suman Kumar Ray
- Independent Researcher, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh-462020, India
| | - Sukhes Mukherjee
- Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh-462020, India
| |
Collapse
|
|
30
|
Chaleshi V, Asadzadeh Aghdaei H, Nourian M, Iravani S, Jalaeikhoo H, Rajaeinejad M, Khoshdel AR, Naghoosi H. Association of MALAT1 expression in gastric carcinoma and the significance of its clinicopathologic features in an Iranian patient. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2021; 14:108-114. [PMID: 33968337 PMCID: PMC8101524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/29/2020] [Indexed: 02/08/2023]
Abstract
AIM The aim of this study was to evaluate the expression of MALAT1 and the relationship between its expression with clinical characteristics in an Iranian gastric cancer patient. BACKGROUND Long non-coding RNAs (LncRNAs) play critical roles in the initiation and development of gastric cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA and plays key roles in various types of human cancer. However, our understanding of the role of lncRNAs in the occurrence and development of gastric cancer is not fully clear. METHODS This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA MALAT1 gene was assessed using quantitative Real-time polymerase chain reaction. B2M was used as an internal control. The 2 -ΔΔCq method was adopted to determine expression fold changes. RESULTS A significant association was observed between the levels of MALAT1 in gastric tumor tissues compared with normal adjacent tissues (mean= 1.558, p= 0.014). In addition, clinicopathologic data on MALAT1 RNA expression levels in gastric cancer tissues was evaluated. No significant association was observed between the relative expression of MALAT1 and the stage, grade, H. pylori infection, and tumor size groups among gastric cancer patients (p= 0.82, p= 0.904, p= 0.407, and p= 0.701, respectively). CONCLUSION The current results showed that MALAT1 has a significant association in gastric cancer. The expression of MALAT1 may be used as a diagnostic biomarker for monitoring gastric cancer patients.
Collapse
Affiliation(s)
- Vahid Chaleshi
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahyar Nourian
- Mahak Hematology Oncology Research Center (Mahak-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrokh Iravani
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Hasan Jalaeikhoo
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Mohsen Rajaeinejad
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Ali Reza Khoshdel
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Hamed Naghoosi
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
31
|
Cáceres-Durán MÁ, Ribeiro-dos-Santos Â, Vidal AF. Roles and Mechanisms of the Long Noncoding RNAs in Cervical Cancer. Int J Mol Sci 2020; 21:ijms21249742. [PMID: 33371204 PMCID: PMC7766288 DOI: 10.3390/ijms21249742] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/03/2020] [Accepted: 12/10/2020] [Indexed: 02/07/2023] Open
Abstract
Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis. Recently, studies have begun to characterize the aberrant regulation of lncRNAs in CC cells and tissues, including Homeobox transcript antisense RNA (HOTAIR), H19, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), Cervical Carcinoma High-Expressed 1 (CCHE1), Antisense noncoding RNA in the inhibitors of cyclin-dependent kinase 4 (ANRIL), Growth arrest special 5 (GAS5) and Plasmacytoma variant translocation 1 (PVT1). They have been associated with several disease-related processes such as cell growth, cell proliferation, cell survival, metastasis and invasion as well as therapeutic resistance, and are novel potential biomarkers for diagnosis and prognosis in CC. In this review, we summarize the current literature regarding the knowledge we have about the roles and mechanisms of the lncRNAs in cervical neoplasia.
Collapse
Affiliation(s)
- Miguel Ángel Cáceres-Durán
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Graduate Program of Genetics and Molecular Biology, Federal University of Pará, Belém 66075-110, Brazil; (M.Á.C.-D.); (Â.R.-d.-S.)
| | - Ândrea Ribeiro-dos-Santos
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Graduate Program of Genetics and Molecular Biology, Federal University of Pará, Belém 66075-110, Brazil; (M.Á.C.-D.); (Â.R.-d.-S.)
- Graduate Program in Oncology and Medical Sciences, Center of Oncology Researches, Federal University of Pará, Belém 66073-005, Brazil
| | - Amanda Ferreira Vidal
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Graduate Program of Genetics and Molecular Biology, Federal University of Pará, Belém 66075-110, Brazil; (M.Á.C.-D.); (Â.R.-d.-S.)
- Correspondence: ; Tel.: +55-91-3201-7843
| |
Collapse
|
|
32
|
Xia Q, Shu Z, Ye T, Zhang M. Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma. Front Genet 2020; 11:595699. [PMID: 33365048 PMCID: PMC7750531 DOI: 10.3389/fgene.2020.595699] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/13/2020] [Indexed: 12/12/2022] Open
Abstract
As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is the fifth major cause of cancer-associated mortality worldwide. In 90% of cases, HCC develops in the context of liver cirrhosis and chronic hepatitis B virus (HBV) infection is an important etiology for cirrhosis and HCC, accounting for 53% of all HCC cases. To understand the underlying mechanisms of the dynamic chain reactions from normal to HBV infection, from HBV infection to liver cirrhosis, from liver cirrhosis to HCC, we analyzed the blood lncRNA expression profiles from 38 healthy control samples, 45 chronic hepatitis B patients, 46 liver cirrhosis patients, and 46 HCC patients. Advanced machine-learning methods including Monte Carlo feature selection, incremental feature selection (IFS), and support vector machine (SVM) were applied to discover the signature associated with HCC progression and construct the prediction model. One hundred seventy-one key HCC progression-associated lncRNAs were identified and their overall accuracy was 0.823 as evaluated with leave-one-out cross validation (LOOCV). The accuracies of the lncRNA signature for healthy control, chronic hepatitis B, liver cirrhosis, and HCC were 0.895, 0.711, 0.870, and 0.826, respectively. The 171-lncRNA signature is not only useful for early detection and intervention of HCC, but also helpful for understanding the multistage tumorigenic processes of HCC.
Collapse
Affiliation(s)
- Qi Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China.,Zhejiang University, Hangzhou, China
| | - Zheyue Shu
- Zhejiang University, Hangzhou, China.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Ting Ye
- Zhejiang University, Hangzhou, China
| | - Min Zhang
- Zhejiang University, Hangzhou, China.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| |
Collapse
|
|
33
|
PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas. Diagnostics (Basel) 2020; 10:diagnostics10100762. [PMID: 32998396 PMCID: PMC7599931 DOI: 10.3390/diagnostics10100762] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/18/2020] [Accepted: 09/26/2020] [Indexed: 12/18/2022] Open
Abstract
Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in “atypical 1 (IR)” HNSCC clusters, negatively influencing patients’ overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the “atypical 1 (IR)” subtype of HNSCC which influences both viral infection and patients’ survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients’ immune response, while on the other it can be favorable in virus replication.
Collapse
|
|
34
|
Galvão MLTDC, Coimbra EC. Long noncoding RNAs (lncRNAs) in cervical carcinogenesis: New molecular targets, current prospects. Crit Rev Oncol Hematol 2020; 156:103111. [PMID: 33080526 DOI: 10.1016/j.critrevonc.2020.103111] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 07/15/2020] [Accepted: 09/09/2020] [Indexed: 12/11/2022] Open
Abstract
Aberrant expression of lncRNAs has been seen as a key factor in a wide range of diseases including cancer. The role of lncRNAs in cervical cancer has not been clearly explained, and has been the subject of recent studies. In this review, we have compiled an updated list of previously reported lncRNAs and established a general profile of these transcripts in accordance with the role they play in cervical carcinogenesis. Thus, information here includes the influence of lncRNAs on cervical tumorigenic process through a disturbance of cellular activities. Additionally, we described recent discoveries about how HPV contributes to lncRNAs expression in cervical cancer and we summarized exploratory studies of strategies adopted to modulate the expression levels of lncRNAs to treat cervical neoplasia, by drawing attention to radio and chemo-resistance. Finally, this paper provides a broad overview that sets out new research directions about the role of lncRNAs in cervical cancer.
Collapse
Affiliation(s)
- Maria Luiza Tabosa de Carvalho Galvão
- Faculty of Medical Sciences, University of Pernambuco, Brazil; Laboratory of Molecular Biology of Viruses, Biological Sciences Institute, University of Pernambuco, Brazil
| | - Eliane Campos Coimbra
- Laboratory of Molecular Biology of Viruses, Biological Sciences Institute, University of Pernambuco, Brazil.
| |
Collapse
|
|
35
|
Wu Y, Zhang Y, Qin X, Geng H, Zuo D, Zhao Q. PI3K/AKT/mTOR pathway-related long non-coding RNAs: roles and mechanisms in hepatocellular carcinoma. Pharmacol Res 2020; 160:105195. [PMID: 32916254 DOI: 10.1016/j.phrs.2020.105195] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 08/30/2020] [Accepted: 09/03/2020] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide with high prevalence and lethality. The oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is a classic dysregulated pathway involved in the pathogenesis of HCC. However, the underlying mechanism for how PI3K/AKT/mTOR pathway aberrantly activates HCC has not been entirely elucidated. The recognition of the functional roles of long non-coding RNAs (lncRNAs) in PI3K/AKT/mTOR signaling axis sheds light on a new dimension to our understanding of hepatocarcinogenesis. In this review, we comprehensively summarize 67 dysregulated PI3K/AKT/mTOR pathway-related lncRNAs in HCC. Many studies have indicated that the 67 dysregulated lncRNAs show oncogenic or anti-oncogenic effects in HCC by regulation on epigenetic, transcriptional and post-transcriptional levels and they play pivotal roles in the initiation of HCC in diverse biological processes like proliferation, metastasis, drug resistance, radio-resistance, energy metabolism, autophagy and so on. Besides, many of these lncRNAs are associated with clinicopathological features and clinical prognosis in HCC, which may provide a potential future application in the diagnosis and therapy of HCC.
Collapse
Affiliation(s)
- Yuting Wu
- Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
| | - Yingshi Zhang
- Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
| | - Xiaochun Qin
- Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
| | - Haobin Geng
- Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
| | - Daiying Zuo
- Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
| | - Qingchun Zhao
- Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; Department of Pharmacy, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenhe District, Shenyang 110840, China.
| |
Collapse
|
|
36
|
Hua C, Zhu J, Zhang B, Sun S, Song Y, van der Veen S, Cheng H. Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7. Front Genet 2020; 11:819. [PMID: 32849815 PMCID: PMC7419603 DOI: 10.3389/fgene.2020.00819] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 07/08/2020] [Indexed: 12/13/2022] Open
Abstract
High-risk human papillomavirus (HPV) infections are the predominant cause of cervical cancer and its early gene E7 plays an important role in cellular proliferation and cell-cycle progression. While tremendous progress has been made in exploring the molecular mechanisms in late tumorigenesis, many pathways showing how HPV deregulates host gene expression in early inapparent infections and early tumorigenesis still remain undefined. Digital RNA sequencing was performed and a total of 195 differentially expressed genes were identified between the HPV16 E7-transfected NHEKs and control cells (p < 0.05, fold-change > 2). GO enrichment showed that HPV16 E7 primarily affected processes involved in anti-viral and immune responses, while KEGG pathway analysis showed enrichment of gene clusters of associated with HPV infection and MAPK signaling. Of the differentially expressed genes, IFI6, SLC39A9 and ZNF185 showed a strong correlation with tumor progression and patient survival in the OncoLnc database while roles for AKAP12 and DUSP5 in carcinogenesis and poor prognosis have previously been established for other cancer types. Our study identified several novel HPV16 E7-regulated candidate genes with putative functions in tumorigenesis, thus providing new insights into HPV persistence in keratinocytes and early onset of tumorigenesis.
Collapse
Affiliation(s)
- Chunting Hua
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jiang Zhu
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Boya Zhang
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Siyuan Sun
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yinjing Song
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Stijn van der Veen
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Department of Microbiology and Parasitology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hao Cheng
- Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| |
Collapse
|
|
37
|
Zheng J, Pang CH, Du W, Wang L, Sun LG, Xing ZY. An allele of rs619586 polymorphism in MALAT1 alters the invasiveness of meningioma via modulating the expression of collagen type V alpha (COL5A1). J Cell Mol Med 2020; 24:10223-10232. [PMID: 32720739 PMCID: PMC7520290 DOI: 10.1111/jcmm.15637] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/12/2020] [Accepted: 06/25/2020] [Indexed: 12/20/2022] Open
Abstract
The rs619586 polymorphism has been shown to alter the expression of MALAT1, which act as a competing endogenous RNA (ceRNA) against miR‐145. And miR‐145 was found to target COL5A1, the interaction between which was shown to be involved in the pathogenesis of invasive meningioma. In this study, we aimed to explore the effect of rs619586 polymorphism and its underlying molecular mechanism in invasive meningioma. Real‐time PCR and Western Blot analysis were used to study the differentiated expression of miR‐145, MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) and COL5A1 (collagen alpha‐1(V) chain) in tumour/serum samples genotyped as rs619586 AA, AG and GG. Computational analysis and luciferase reporter assay were also conducted to identify the regulatory relationship between miR‐145 and MALAT1/COL5A1. Meanwhile, expression of miR‐145 and COL5A1 in different cell treatment groups was measured to validate the results obtained from earlier experiments. As shown by the results and in tumour/serum samples genotyped as AA, AG and GG, the expression of both MALAT1 and COL5A1 was down‐regulated in a stepwise fashion, while the expression of miR‐145 was increased, suggesting a potential negative relationship between MALAT1/COL5A1 and miR‐145. Meanwhile, miR‐145 was shown to bind to MALAT1, while COL5A1 was identified as a virtual target gene of miR‐145. As a consequence, a MALAT1/miR‐145/COL5A1 molecular pathway was established based on the above results. In particular, with the presence of rs619586 A>G polymorphism, the expression of MALAT1 and COL5A1 was both reduced, leading to reduced invasiveness of meningioma.
Collapse
Affiliation(s)
- Jie Zheng
- Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, China
| | - Chang-He Pang
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Du
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lei Wang
- Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, China
| | - Lai-Guang Sun
- Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, China
| | - Zhen-Yi Xing
- Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, China
| |
Collapse
|
|
38
|
Zhao C, Liu J, Wu H, Hu J, Chen J, Chen J, Qiao F. Aberrant methylation-mediated downregulation of lncRNA CCND2 AS1 promotes cell proliferation in cervical cancer. ACTA ACUST UNITED AC 2020; 27:11. [PMID: 32607313 PMCID: PMC7318366 DOI: 10.1186/s40709-020-00122-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 06/19/2020] [Indexed: 12/27/2022]
Abstract
Background Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. The lncRNA CCND2 AS1 has been shown to be involved in the growth of several tumors; however, its role in cervical cancer has not been elucidated. This study aimed to explore the expression, function, and underlying mechanism of action of CCND2 AS1 in cervical cancer. Expression of CCND2 AS1 was examined in cervical cancer and adjacent normal cervical tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and by bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) database. The function of CCND2 AS1 was investigated by overexpressing or silencing CCND2 AS1 in HeLa and SiHa cervical cancer cells followed by in vitro and in vivo analyses. Methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) were used to detect CCND2 AS1 promoter methylation status in cervical cancer cells. Results CCND2 AS1 expression was lower in cervical cancer compared with normal cervical tissues, and the level was significantly correlated with the patient age and tumor size. CCND2 AS1 overexpression inhibited the proliferation and cell cycle progression of HeLa cells in vitro and/or in vivo, whereas CCND2 AS1 silencing had the opposite effects. CCND2 AS1 expression was elevated after treatment of cervical cancer cells with the DNA methyltransferase inhibitor 5′-azacytidine (5′-Aza), and this was mediated, at least in part, via reduced CpG methylation at the CCND2 AS1 promoter. Conclusion CCND2 AS1 expression is downregulated in cervical cancer, potentially through increased CCND2 AS1 promoter methylation, and the upregulation of CCND2 AS1 expression inhibited tumor growth. These data suggest that CCND2 AS1 could be a diagnostic marker and potential therapeutic target for cervical cancer.
Collapse
Affiliation(s)
- Chengcheng Zhao
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.,Central Laboratory, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Liu
- Department of Oncology Gynecology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Huazhang Wu
- School of Life Sciences, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China
| | - Jiaojiao Hu
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China
| | - Jianquan Chen
- Central Laboratory, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Jie Chen
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China
| | - Fengchang Qiao
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China
| |
Collapse
|
|
39
|
Casarotto M, Fanetti G, Guerrieri R, Palazzari E, Lupato V, Steffan A, Polesel J, Boscolo-Rizzo P, Fratta E. Beyond MicroRNAs: Emerging Role of Other Non-Coding RNAs in HPV-Driven Cancers. Cancers (Basel) 2020; 12:cancers12051246. [PMID: 32429207 PMCID: PMC7281476 DOI: 10.3390/cancers12051246] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 05/11/2020] [Accepted: 05/12/2020] [Indexed: 12/11/2022] Open
Abstract
Persistent infection with high-risk Human Papilloma Virus (HPV) leads to the development of several tumors, including cervical, oropharyngeal, and anogenital squamous cell carcinoma. In the last years, the use of high-throughput sequencing technologies has revealed a number of non-coding RNA (ncRNAs), distinct from micro RNAs (miRNAs), that are deregulated in HPV-driven cancers, thus suggesting that HPV infection may affect their expression. However, since the knowledge of ncRNAs is still limited, a better understanding of ncRNAs biology, biogenesis, and function may be challenging for improving the diagnosis of HPV infection or progression, and for monitoring the response to therapy of patients affected by HPV-driven tumors. In addition, to establish a ncRNAs expression profile may be instrumental for developing more effective therapeutic strategies for the treatment of HPV-associated lesions and cancers. Therefore, this review will address novel classes of ncRNAs that have recently started to draw increasing attention in HPV-driven tumors, with a particular focus on ncRNAs that have been identified as a direct target of HPV oncoproteins.
Collapse
Affiliation(s)
- Mariateresa Casarotto
- Division of Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy; (M.C.); (R.G.); (A.S.)
| | - Giuseppe Fanetti
- Division of Radiotherapy, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy; (G.F.); (E.P.)
| | - Roberto Guerrieri
- Division of Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy; (M.C.); (R.G.); (A.S.)
| | - Elisa Palazzari
- Division of Radiotherapy, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy; (G.F.); (E.P.)
| | - Valentina Lupato
- Division of Otolaryngology, General Hospital “Santa Maria degli Angeli”, 33170 Pordenone, Italy;
| | - Agostino Steffan
- Division of Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy; (M.C.); (R.G.); (A.S.)
| | - Jerry Polesel
- Division of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy;
| | - Paolo Boscolo-Rizzo
- Section of Otolaryngology, Department of Neurosciences, University of Padova, 31100 Treviso, Italy;
| | - Elisabetta Fratta
- Division of Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy; (M.C.); (R.G.); (A.S.)
- Correspondence: ; Tel.: +390434659569
| |
Collapse
|
|
40
|
Hao Y, Yan Z, Zhang A, Hu S, Wang N, Luo XG, Ma W, Zhang TC, He H. IL-6/STAT3 mediates the HPV18 E6/E7 stimulated upregulation of MALAT1 gene in cervical cancer HeLa cells. Virus Res 2020; 281:197907. [DOI: 10.1016/j.virusres.2020.197907] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 01/23/2020] [Accepted: 02/26/2020] [Indexed: 12/25/2022]
|
|
41
|
Sharma S, Munger K. The Role of Long Noncoding RNAs in Human Papillomavirus-associated Pathogenesis. Pathogens 2020; 9:pathogens9040289. [PMID: 32326624 PMCID: PMC7238103 DOI: 10.3390/pathogens9040289] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 04/13/2020] [Accepted: 04/14/2020] [Indexed: 12/15/2022] Open
Abstract
Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack intrinsic enzymatic activities and they function by binding to cellular regulatory molecules, thereby subverting normal cellular homeostasis. Much effort has focused on identifying protein targets of the E6 and E7 proteins, but it has been estimated that ~98% of the human transcriptome does not encode proteins. There is a growing interest in studying noncoding RNAs as biochemical targets and biological mediators of human papillomavirus (HPV) E6/E7 oncogenic activities. This review focuses on HPV E6/E7 targeting cellular long noncoding RNAs, a class of biologically versatile molecules that regulate almost every known biological process and how this may contribute to viral oncogenesis.
Collapse
|
|
42
|
Tornesello ML, Faraonio R, Buonaguro L, Annunziata C, Starita N, Cerasuolo A, Pezzuto F, Tornesello AL, Buonaguro FM. The Role of microRNAs, Long Non-coding RNAs, and Circular RNAs in Cervical Cancer. Front Oncol 2020; 10:150. [PMID: 32154165 PMCID: PMC7044410 DOI: 10.3389/fonc.2020.00150] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 01/28/2020] [Indexed: 12/24/2022] Open
Abstract
Prolonged infection of uterine cervix epithelium with human papillomavirus (HPV) and constitutive expression of viral oncogenes have been recognized as the main cause of the complex molecular changes leading to transformation of cervical epithelial cells. Deregulated expression of microRNAs (miRNA), long non-coding RNAs (lncRNA), and circular RNAs (circRNA) is involved in the initiation and promotion processes of cervical cancer development. Expression profiling of small RNAs in cervical neoplasia revealed up-regulated "oncogenic" miRNAs, such as miR-10a, miR-21, miR-19, and miR-146a, and down regulated "tumor suppressive" miRNAs, including miR-29a, miR-372, miR-214, and miR-218, associated with cell growth, malignant transformation, cell migration, and invasion. Also several lncRNAs, comprising among others HOTAIR, MALAT1, GAS5, and MEG3, have shown to be associated with various pathogenic processes such as tumor progression, invasion as well as therapeutic resistance and emerged as new diagnostic and prognostic biomarkers in cervical cancer. Moreover, human genes encoded circular RNAs, such as has_circ-0018289, have shown to sponge specific miRNAs and to concur to the deregulation of target genes. Viral encoded circE7 has also demonstrated to overexpress E7 oncoprotein thus contributing to cell transformation. In this review, we summarize current literature on the complex interplay between miRNAs, lncRNAs, and circRNAs and their role in cervical neoplasia.
Collapse
Affiliation(s)
- Maria Lina Tornesello
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Raffaella Faraonio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy
| | - Luigi Buonaguro
- Cancer Immunoregulation Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Clorinda Annunziata
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Noemy Starita
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Andrea Cerasuolo
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Francesca Pezzuto
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Anna Lucia Tornesello
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| | - Franco Maria Buonaguro
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy
| |
Collapse
|
|
43
|
Arredondo-Robles AV, Rodríguez-López KP, Ávila-Avilés RD. RETRACTED ARTICLE: Long non-coding RNAs in cervical cancer. J Appl Genet 2020; 61:405. [PMID: 31981186 DOI: 10.1007/s13353-020-00545-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 01/03/2020] [Accepted: 01/20/2020] [Indexed: 10/25/2022]
Affiliation(s)
- A V Arredondo-Robles
- Facultad de Ciencias, Universidad Autónoma del Estado de México, Campus El Cerrillo, Piedras Blancas, Carretera Toluca Kilómetro 15.5, C.P. 50200, Ixtlahuaca, Edo. de México, Mexico
| | - K P Rodríguez-López
- Facultad de Ciencias, Universidad Autónoma del Estado de México, Campus El Cerrillo, Piedras Blancas, Carretera Toluca Kilómetro 15.5, C.P. 50200, Ixtlahuaca, Edo. de México, Mexico
| | - R D Ávila-Avilés
- Facultad de Ciencias, Universidad Autónoma del Estado de México, Campus El Cerrillo, Piedras Blancas, Carretera Toluca Kilómetro 15.5, C.P. 50200, Ixtlahuaca, Edo. de México, Mexico. .,Departamento de Genética y Biología Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av Instituto Politécnico Nacional, 2508, La Laguna Ticoman, C.P. 07360, Ciudad de México, Mexico.
| |
Collapse
|
|
44
|
Lv R, Zhang QW. The long noncoding RNA FTH1P3 promotes the proliferation and metastasis of cervical cancer through microRNA‑145. Oncol Rep 2019; 43:31-40. [PMID: 31789421 PMCID: PMC6908927 DOI: 10.3892/or.2019.7413] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 08/09/2019] [Indexed: 12/12/2022] Open
Abstract
Emerging evidence has revealed that long noncoding RNAs (lncRNAs) play crucial roles in the development and progression of tumors. The present study aimed to examine the roles and illustrate the underlying mechanisms of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) in cervical cancer. The expression of lncRNA FTH1P3 and microRNA-145 (miRNA-145 or miR-145) in human cervical cancer samples and cervical cancer cell lines was detected by qRT-PCR (reverse transcription-quantitative polymerase chain reaction). FTH1P3 overexpression, siRNA plasmid, hsa-miR-145 mimic or hsa-miR-145 inhibitor were transfected. The target of FTH1P3 was predicted by bioinformatics analysis and validated by luciferase assay. Statistical significance analysis was performed by SPSS software. The results revealed that FTH1P3 was significantly upregulated in cervical cancer tissues compared with normal tissues. Increased expression of FTH1P3 was revealed in human cervical cancer cell lines compared with cervical normal epithelial cells. Downregulation of FTH1P3 inhibited cell proliferation, invasion and migration, and promoted apoptosis in cervical cancer cells. miR-145 was predicted and validated as a direct target of FTH1P3. Moreover, FTH1P3 siRNA partially attenuated the effects of the miR-145 inhibitor on cell viability and mobility in cervical cancer cells. The present results demonstrated that lncRNA FTH1P3 functioned as a promoting factor in cervical cancer by targeting miR-145.
Collapse
Affiliation(s)
- Rui Lv
- Department of Gynecological Oncology Ward, Gansu Provincial Cancer Hospital, Lanzhou, Gansu 730050, P.R. China
| | - Qian Wen Zhang
- Department of Gynecological Oncology Ward, Gansu Provincial Cancer Hospital, Lanzhou, Gansu 730050, P.R. China
| |
Collapse
|
|
45
|
Metastasis Associated Lung Adenocarcinoma Transcript 1: An update on expression pattern and functions in carcinogenesis. Exp Mol Pathol 2019; 112:104330. [PMID: 31712117 DOI: 10.1016/j.yexmp.2019.104330] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 11/03/2019] [Indexed: 12/28/2022]
Abstract
The Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is among long non-coding RNAs (lncRNAs) which has disapproved the old term of "junk DNA" which was used for majority of human genome which are not transcribed to proteins. An extensive portion of literature points to the fundamental role of this lncRNA in tumorigenesis process of diverse cancers ranging from solid tumors to leukemia. Being firstly identified in lung cancer, it has prognostic and diagnostic values in several cancer types. Consistent with the proposed oncogenic roles for this lncRNA, most of studies have shown up-regulation of MALAT1 in malignant tissues compared with non-malignant/normal tissues of the same source. However, few studies have shown down-regulation of MALAT1 in breast cancer, endometrial cancer, colorectal cancer and glioma. In the current study, we have conducted a comprehensive literature search and provided an up-date on the role of MALAT1 in cancer biology. Our investigation underscores a potential role as a diagnostic/prognostic marker and a putative therapeutic target for MALAT1.
Collapse
|
|
46
|
Jia M, Ren L, Hu L, Ma H, Jin G, Li D, Li N, Hu Z, Hang D. Association of long non-coding RNA HOTAIR and MALAT1 variants with cervical cancer risk in Han Chinese women. J Biomed Res 2019; 33:308. [PMCID: PMC6813535 DOI: 10.7555/jbr.33.20180096] [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: 10/01/2018] [Accepted: 02/26/2019] [Indexed: 05/05/2024] Open
Abstract
Long noncoding RNA (lncRNA) HOTAIR and MALAT1 are implicated in the development of multiple cancers. Genetic variants within HOTAIR and MALAT1 may affect the gene expression, thereby modifying genetic susceptibility to cervical cancer. A case-control study was designed, including 1 486 cervical cancer patients and 1 536 healthy controls. Based on RegulomeDB database, 11 SNPs were selected and genotyped by using Sequenom's Mass ARRAY. Univariate and multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI). We found that the A allele of rs35643724 in HOTAIR was associated with increased risk of cervical cancer, while the C allele of rs1787666 in MALAT1 was associated with decreased risk. Compared to individuals with 0–1 unfavorable allele, those with 3–4 unfavorable alleles showed 18% increased odds of having cervical cancer. Our findings suggest that HOTAIR rs35643724 and MALAT1 rs1787666 might represent potential biomarkers for cervical cancer susceptibility.
Collapse
Affiliation(s)
- Meiqun Jia
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Department of Gynecologic Oncology, the Affiliated Tumor Hospital of Nantong University (Nantong Tumor Hospital), Nantong, Jiangsu 226361, China
| | - Lulu Ren
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Lingmin Hu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Department of Reproduction, the Affiliated Changzhou Maternity and Child Health Care Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China
| | - Hongxia Ma
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Guangfu Jin
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Dake Li
- Department of Gynecologic Oncology, Nanjing Maternity and Child Health Hospital, Nanjing, Jiangsu 210004, China
| | - Ni Li
- Program Office for Cancer Screening in Urban China, National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhibin Hu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Dong Hang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China
| |
Collapse
|
|
47
|
Yao Z, Zhang Y, Xu D, Zhou X, Peng P, Pan Z, Xiao N, Yao J, Li Z. Research Progress on Long Non-Coding RNA and Radiotherapy. Med Sci Monit 2019; 25:5757-5770. [PMID: 31375656 PMCID: PMC6690404 DOI: 10.12659/msm.915647] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNAs (lncRNAs), a group of non-protein-coding RNAs longer than 200 nucleotides, are involved in multiple biological and pathological processes, such as proliferation, apoptosis, migration, invasion, angiogenesis, and immune escape. Many studies have shown that lncRNAs participate in the complex network of cancer and play vital roles as oncogenes or tumor-suppressor genes in a variety of cancers. Moreover, recent research has shown that abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy may participate in the progression of cancers and affect the radiation sensitivity of malignant tumor cells mediated by specific signaling pathways or cell cycle regulation. In this review, we summarize the published studies on lncRNAs in radiotherapy regarding the biological function and mechanism of human cancers, including esophageal cancer, pancreatic cancers, nasopharyngeal carcinoma, hepatocellular carcinoma, cervical cancer, colorectal cancer, and gastric cancer.
Collapse
Affiliation(s)
- Zhifeng Yao
- Department of Radiotherapy, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (mainland).,Department of Oncology, The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China (mainland)
| | - Yiwen Zhang
- Department of Nursing, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (mainland)
| | - Danghui Xu
- Department of Medical Imaging, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China (mainland)
| | - Xuejun Zhou
- Department of Medical Imaging, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China (mainland)
| | - Peng Peng
- Department of Nursing, Nanjing Health Higher Vocational and Technical College, Nanjing, Jiangsu, China (mainland)
| | - Zhiyao Pan
- Department of Basic Medicine, Zhejiang University Medical College, Hangzhou, Zhejiang, China (mainland)
| | - Nan Xiao
- Department of Medical Imaging, Nanjing Health Higher Vocational and Technical College, Nanjing, Jiangsu, China (mainland)
| | - Jianxin Yao
- Department of Medical Imaging, Nanjing Health Higher Vocational and Technical College, Nanjing, Jiangsu, China (mainland)
| | - Zhifeng Li
- Department of Medical Imaging, Nanjing Health Higher Vocational and Technical College, Nanjing, Jiangsu, China (mainland)
| |
Collapse
|
|
48
|
Shen F, Zheng H, Zhou L, Li W, Xu X. Overexpression of MALAT1 contributes to cervical cancer progression by acting as a sponge of miR-429. J Cell Physiol 2019; 234:11219-11226. [PMID: 30515786 DOI: 10.1002/jcp.27772] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 10/30/2018] [Indexed: 01/22/2023]
Abstract
Cervical cancer remains a malignant type of tumor and is the fourth leading cause of cancer-related death among females. MALAT1 has been identified as a tumor oncogene in various cancers. Our present study aimed to explore the biological role of MALAT1 in cervical cancer. We observed that MALAT1 was significantly upregulated in human cervical cancer cell lines compared with the ectocervical epithelial cells. MALAT1 was repressed by transfection with LV-shMALAT1, whereas increased by LV-MALAT1 in HeLa and Caski cells. Silencing of MALAT1 obviously reduced cervical cell viability, induced cell apoptosis, and repressed cell invasion capacity. Conversely, overexpression of MALAT1 exhibited an opposite phenomenon. Furthermore, miR-429 was predicted as a direct target of MALAT1, and it was dramatically decreased in cervical cancer cells. It has been shown that miR-429 plays a crucial role in cervical cancer progression. In our current study, the targeting correlation between MALAT1 and miR-429 was confirmed by luciferase reporter assays and RIP experiments. Finally, in vivo animal models were established, and we indicated that MALAT1 inhibited cervical cancer progression via targeting miR-429. These findings revealed that MALAT1 can sponge miR-429 and regulate cervical cancer pathogenesis in vivo and in vitro. In conclusion, we indicated that the MALAT1/miR-429 axis was involved in cervical cancer development.
Collapse
Affiliation(s)
- Fujin Shen
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hongyun Zheng
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China
| | - Limei Zhou
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Li
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xuexian Xu
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| |
Collapse
|
|
49
|
LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling. Anticancer Drugs 2019; 29:725-735. [PMID: 29916897 DOI: 10.1097/cad.0000000000000650] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay. Western blot was used to detect the expression levels of epithelial-mesenchymal transition proteins and Akt/mTOR key components after treatment. Dual luciferase reporter assay coupled with qRT-PCR was used to verify the direct interaction between MALAT1 and miR-206. MALAT1 was significantly up-regulated in both NSCLC tissues and cell lines. High expression of MALAT1 correlated positively with tumor size and lymphatic metastasis in NSCLC, whereas no correlation was found between MALAT1 expression and sex, age, clinical stage, and histological grade. We also showed that MALAT1 promoted epithelial-mesenchymal transition, cell migration, and invasion by activating Akt/mTOR signaling in A549 and H1299 cells. miR-206 was a direct downstream target of MALAT1 in NSCLC. MALAT1 promoted cell migration and invasion by sponging miR-206 in NSCLC cells. In addition, miR-206 inhibited MALAT1-mediated activation of Akt/mTOR signaling in A549 and H1299 cells. lncRNA MALAT1 promotes migration and invasion of NSCLC by targeting miR-206 and activating Akt/mTOR signaling.
Collapse
|
|
50
|
TNF-α-induced lncRNA LOC105374902 promotes the malignant behavior of cervical cancer cells by acting as a sponge of miR-1285-3p. Biochem Biophys Res Commun 2019; 513:56-63. [DOI: 10.1016/j.bbrc.2019.03.079] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 03/14/2019] [Indexed: 12/16/2022]
|