|
1
|
Muge Q, Qing Y, Bao W, Bao X, Gaowa A, Chen L. LncRNA CCAT1 decreases the sensitivity to doxorubicin in lung cancer cells by regulating miR-181a/CPEB2 axis. Med Oncol 2025; 42:109. [PMID: 40089944 DOI: 10.1007/s12032-025-02668-7] [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: 12/25/2024] [Accepted: 03/04/2025] [Indexed: 03/18/2025]
Abstract
Recently, long non-coding RNAs have gained an increasing amount of attention in treating lung cancer. However, a full understanding of how CCAT1 lncRNA works against proliferation is not yet available. Therefore, we assess the impact of CCAT1 on the lung cancer cell proliferation, apoptosis, and doxorubicin (DOX) sensitivity, and the involvement of miR-181a/CPEB2 pathway. For this purpose, lung cancer A549 cells were exposed to siRNA against CCAT1 and DOX and cell viability were measured by MTT assay. ELISA was used to evaluate cell apoptosis. The protein and mRNA expression levels of apoptotic markers, miR-181a and CPEB2 were measured by western blot and qRT-PCR. Knock-downing CCAT1 inhibited the cell viability of A549 cells. In addition, si-CCAT1 treatment increased apoptosis in both cell lines via modulating the anti- and pro-apoptotic markers. Si-CCAT1 increased the levels miR-181a and decreased CPEB2 in A549 cells. In conclusion, our study has provided strong evidence that lncRNA CCAT1 decreased the sensitivity to doxorubicin in lung cancer cells by regulating the miR-181a/CPEB2 axis.
Collapse
Affiliation(s)
- Qi Muge
- School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China
- The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, 028000, Inner Mongolia, China
| | - Yu Qing
- The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, 028000, Inner Mongolia, China
| | - Wenshan Bao
- The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, 028000, Inner Mongolia, China
| | - Xiangrong Bao
- Inner Mongolia University for Nationalities, Tongliao, 028000, China
| | - Arong Gaowa
- Inner Mongolia University for Nationalities, Tongliao, 028000, China
| | - Lanying Chen
- National Engineering Research Center of Traditional Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
| |
Collapse
|
|
2
|
Wang S, Bai Y, Ma J, Qiao L, Zhang M. Long non-coding RNAs: regulators of autophagy and potential biomarkers in therapy resistance and urological cancers. Front Pharmacol 2024; 15:1442227. [PMID: 39512820 PMCID: PMC11540796 DOI: 10.3389/fphar.2024.1442227] [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: 06/01/2024] [Accepted: 10/14/2024] [Indexed: 11/15/2024] Open
Abstract
The non-coding RNAs (ncRNAs) comprise a large part of human genome that mainly do not code for proteins. Although ncRNAs were first believed to be non-functional, the more investigations highlighted tthe possibility of ncRNAs in controlling vital biological processes. The length of long non-coding RNAs (lncRNAs) exceeds 200 nucleotidesand can be present in nucleus and cytoplasm. LncRNAs do not translate to proteins and they have been implicated in the regulation of tumorigenesis. On the other hand, One way cells die is by a process called autophagy, which breaks down proteins and other components in the cytoplasm., while the aberrant activation of autophagy allegedly involved in the pathogenesis of diseases. The autophagy exerts anti-cancer activity in pre-cancerous lesions, while it has oncogenic function in advanced stages of cancers. The current overview focuses on the connection between lncRNAs and autophagy in urological cancers is discussed. Notably, one possible role for lncRNAs is as diagnostic and prognostic variablesin urological cancers. The proliferation, metastasis, apoptosis and therapy response in prostate, bladder and renal cancers are regulated by lncRNAs. The changes in autophagy levels can also influence the apoptosis, proliferation and therapy response in urological tumors. Since lncRNAs have modulatory functions, they can affect autophagy mechanism to determine progression of urological cancers.
Collapse
Affiliation(s)
- Shizong Wang
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Yang Bai
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Jie Ma
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Liang Qiao
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Mingqing Zhang
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| |
Collapse
|
|
3
|
Maqbool M, Hussain MS, Bisht AS, Kumari A, Kamran A, Sultana A, Kumar R, Khan Y, Gupta G. Connecting the dots: LncRNAs in the KRAS pathway and cancer. Pathol Res Pract 2024; 262:155570. [PMID: 39226802 DOI: 10.1016/j.prp.2024.155570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/17/2024] [Accepted: 08/28/2024] [Indexed: 09/05/2024]
Abstract
Long non-coding RNAs (lncRNAs) have been identified as important participants in several biological functions, particularly their complex interactions with the KRAS pathway, which provide insights into the significant roles lncRNAs play in cancer development. The KRAS pathway, a central signaling cascade crucial for cell proliferation, survival, and differentiation, stands out as a key therapeutic target due to its aberrant activation in many human cancers. Recent investigations have unveiled a myriad of lncRNAs, such as H19, ANRIL, and MEG3, intricately modulating the KRAS pathway, influencing both its activation and repression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional control. These lncRNAs function as fine-tuners, delicately orchestrating the balance required for normal cellular function. Their dysregulation has been linked to the development and progression of multiple malignancies, including lung, pancreatic, and colorectal carcinomas, which frequently harbor KRAS mutations. This scrutiny delves into the functional diversity of specific lncRNAs within the KRAS pathway, elucidating their molecular mechanisms and downstream effects on cancer phenotypes. Additionally, it underscores the diagnostic and prognostic potential of these lncRNAs as indicators for cancer detection and assessment. The complex regulatory network that lncRNAs construct within the context of the KRAS pathway offers important insights for the creation of focused therapeutic approaches, opening new possibilities for precision medicine in oncology. However, challenges such as the dual roles of lncRNAs in different cancer types and the difficulty in therapeutically targeting these molecules highlight the ongoing debates and need for further research. As ongoing studies unveil the complexities of lncRNA-mediated KRAS pathway modulation, the potential for innovative cancer interventions becomes increasingly promising.
Collapse
Affiliation(s)
- Mudasir Maqbool
- Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, India
| | - Md Sadique Hussain
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand 248007, India.
| | - Ajay Singh Bisht
- School of Pharmaceutical Sciences, Shri Guru Ram Rai University, Patel Nagar, Dehradun, Uttarakhand 248001, India
| | - Alka Kumari
- University institute of pharmacy, Chandigarh University, Gharaun, Punjab 140413, India
| | - Almaz Kamran
- HIMT College of Pharmacy, Plot No. 08, Knowledge Park - 1, Greater Noida, Uttar Pradesh 201310, India
| | - Ayesha Sultana
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya University, Deralakatte, Mangalore, Karnataka, India
| | - Rajesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Yumna Khan
- Institute of Biotechnology and Genetic Engineering (Health Division), The University of Agriculture, Peshawar, Khyber Pakhtunkhwa 25000, Pakistan
| | - Gaurav Gupta
- Centre for Research Impact & Outcome-Chitkara College of Pharmacy, Chitkara University, Punjab, India; Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| |
Collapse
|
|
4
|
Ghorbani A, Hosseinie F, Khorshid Sokhangouy S, Islampanah M, Khojasteh-Leylakoohi F, Maftooh M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Nazari E, Avan A. The prognostic, diagnostic, and therapeutic impact of Long noncoding RNAs in gastric cancer. Cancer Genet 2024; 282-283:14-26. [PMID: 38157692 DOI: 10.1016/j.cancergen.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 11/27/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.
Collapse
Affiliation(s)
- Atousa Ghorbani
- Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Hosseinie
- Department of Nursing, Faculty of Nursing and Midwifery, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Saeideh Khorshid Sokhangouy
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Muhammad Islampanah
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Nazari
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
5
|
Cheng C, Liu Z, Liu D, Chen H, Wang Y, Sun B. LncRNA CCAT1 participates in pancreatic ductal adenocarcinoma progression by forming a positive feedback loop with c-Myc. Carcinogenesis 2024; 45:69-82. [PMID: 37936306 DOI: 10.1093/carcin/bgad076] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 10/29/2023] [Accepted: 11/02/2023] [Indexed: 11/09/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) play fundamental roles in cancer development; however, the underlying mechanisms for a large proportion of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) have not been elucidated. The expression of colon cancer-associated transcript-1 (CCAT1) in PDAC specimens and cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The function of CCAT1 was examined in vitro and in vivo. The interactions among CCAT1, miR-24-3p and c-Myc were determined by bioinformatics analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, and rescue experiments. CCAT1 was significantly increased in PDAC, positively correlated with PDAC progression and predicted a worse prognosis. Furthermore, CCAT1 enhanced Adenosine triphosphate (ATP) production to facilitate PDAC cell proliferation, colony formation and motility in vitro and tumor growth in vivo. CCAT1 may serve as an miR-24-3p sponge, thereby counteracting its repression by c-Myc expression. Reciprocally, c-Myc may act as a transcription factor to alter CCAT1 expression by directly targeting its promoter region, thus forming a positive feedback loop with CCAT1. Collectively, these results demonstrate that a positive feedback loop of CCAT1/miR-24-3p/c-Myc is involved in PDAC development, which may serve as a biomarker and therapeutic target for PDAC.
Collapse
Affiliation(s)
- Chundong Cheng
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
| | - Zonglin Liu
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
| | - Danxi Liu
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
| | - Hua Chen
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
| | - Yongwei Wang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China
| |
Collapse
|
|
6
|
Alharthi NS, Al-Zahrani MH, Hazazi A, Alhuthali HM, Gharib AF, Alzahrani S, Altalhi W, Almalki WH, Khan FR. Exploring the lncRNA-VEGF axis: Implications for cancer detection and therapy. Pathol Res Pract 2024; 253:154998. [PMID: 38056133 DOI: 10.1016/j.prp.2023.154998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/16/2023] [Accepted: 11/27/2023] [Indexed: 12/08/2023]
Abstract
Cancer is a complicated illness that spreads indefinitely owing to epigenetic, genetic, and genomic alterations. Cancer cell multidrug susceptibility represents a severe barrier in cancer therapy. As a result, creating effective therapies requires a better knowledge of the mechanisms driving cancer development, progress, and resistance to medications. The human genome is predominantly made up of long non coding RNAs (lncRNAs), which are currently identified as critical moderators in a variety of biological functions. Recent research has found that changes in lncRNAs are closely related to cancer biology. The vascular endothelial growth factor (VEGF) signalling system is necessary for angiogenesis and vascular growth and has been related to an array of health illnesses, such as cancer. LncRNAs have been identified to alter a variety of cancer-related processes, notably the division of cells, movement, angiogenesis, and treatment sensitivity. Furthermore, lncRNAs may modulate immune suppression and are being investigated as possible indicators for early identification of cancer. Various lncRNAs have been associated with cancer development and advancement, serving as cancer-causing or suppressing genes. Several lncRNAs have been demonstrated through research to impact the VEGF cascade, resulting in changes in angiogenesis and tumor severity. For example, the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to foster the formation of oral squamous cell carcinoma and the epithelial-mesenchymal transition by stimulating the VEGF-A and Notch systems. Plasmacytoma variant translocation 1 (PVT1) promotes angiogenesis in non-small-cell lung cancer by affecting miR-29c and boosting the VEGF cascade. Furthermore, lncRNAs regulate VEGF production and angiogenesis by interacting with multiple downstream signalling networks, including Wnt, p53, and AKT systems. Identifying how lncRNAs engage with the VEGF cascade in cancer gives beneficial insights into tumor biology and possible treatment strategies. Exploring the complicated interaction between lncRNAs and the VEGF pathway certainly paves avenues for novel ways to detect better accurately, prognosis, and cure cancers. Future studies in this area could open avenues toward the creation of innovative cancer therapy regimens that enhance the lives of patients.
Collapse
Affiliation(s)
- Nahed S Alharthi
- Department of Medical Laboratory, College of Applied Medical Sciences in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudia Arabia
| | | | - Ali Hazazi
- Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Hayaa Moeed Alhuthali
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Amal F Gharib
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Shatha Alzahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Wafa Altalhi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Farhan R Khan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences AlQuwayiyah, Shaqra University, Saudi Arabia.
| |
Collapse
|
|
7
|
Fahmy S, Ramzy A, El Samaloty NM, Sedky NK, Azzazy HMES. PEGylated Chitosan Nanoparticles Loaded with Betaine and Nedaplatin Hamper Breast Cancer: In Vitro and In Vivo Studies. ACS OMEGA 2023; 8:41485-41494. [PMID: 37969975 PMCID: PMC10633871 DOI: 10.1021/acsomega.3c05359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 10/06/2023] [Indexed: 11/17/2023]
Abstract
The current study investigates the anticancer effects of PEGylated chitosan nanoparticles (CS NPs) coloaded with betaine (BT) and nedaplatin (ND) on breast adenocarcinoma (MCF-7) cells and breast cancer-bearing rats. Hereof, the ionotropic gelation approach was implemented for the synthesis of PEG-uncoated and PEG-coated CS NPs encompassing either BT, ND, or both (BT-ND). The sizes of the developed BT/CS NPs, ND/CS NPs, and BT-ND/CS NPs were 176.84 ± 7.45, 204.1 ± 13.6, and 201.1 ± 23.35 nm, respectively. Meanwhile, the sizes of the synthesized BT/PEG-CS NPs, ND/PEG-CS NPs, and BT-ND/PEG-CS NPs were 165.1 ± 32.40, 148.2 ± 20.98, and 143.7 ± 7.72 nm, respectively. The surface charges of the fabricated nanoparticles were considerably high. All of the synthesized nanoparticles displayed a spherical form and significant entrapment efficiency. Release experiments demonstrated that the PEGylated and non-PEGylated CS NPs could discharge their contents into the tumor cells' microenvironments (pH 5.5). In addition, the NPs demonstrated an outstanding ability to reduce the viability of the MCF-7 cell line. In addition, BT-ND/PEG-CS NPs were found to be the strongest among all NP preparations, where they caused around 90% decrease in the size of mammary gland tumors in rats compared to vehicle-treated animals.
Collapse
Affiliation(s)
- Sherif
Ashraf Fahmy
- Department
of Chemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative
Capital, Cairo 11835, Egypt
| | - Asmaa Ramzy
- Department
of Chemistry, School of Sciences & Engineering, The American University in Cairo, AUC Avenue, P.O. Box 74, New Cairo 11835, Egypt
| | - Nourhan M. El Samaloty
- Biochemistry
Department, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo 11786, Egypt
- Pharmacology
and Biochemistry Department, Faculty of Pharmaceutical Sciences and
Pharmaceutical Industries, Future University
in Egypt, Cairo 12311, Egypt
| | - Nada K. Sedky
- Department
of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative
Capital, Cairo 11835, Egypt
| | - Hassan Mohamed El-Said Azzazy
- Department
of Chemistry, School of Sciences & Engineering, The American University in Cairo, AUC Avenue, P.O. Box 74, New Cairo 11835, Egypt
- Department
of Nanobiophotonics, Leibniz Institute of
Photonic Technology, Albert Einstein Str. 9, Jena 07745, Germany
| |
Collapse
|
|
8
|
Liu W, Zuo B, Liu W, Huo Y, Zhang N, Yang M. Long non-coding RNAs in non-small cell lung cancer: implications for preventing therapeutic resistance. Biochim Biophys Acta Rev Cancer 2023; 1878:188982. [PMID: 37734560 DOI: 10.1016/j.bbcan.2023.188982] [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: 06/21/2023] [Revised: 08/14/2023] [Accepted: 08/15/2023] [Indexed: 09/23/2023]
Abstract
Lung cancer has the highest mortality and morbidity rates among all cancers worldwide. Despite many complex treatment options, including radiotherapy, chemotherapy, targeted drugs, immunotherapy, and combinations of these treatments, efficacy is low in cases of resistance to therapy, metastasis, and advanced disease, contributing to low overall survival. There is a pressing need for the discovery of novel biomarkers and therapeutic targets for the early diagnosis of lung cancer and to determine the efficacy and outcomes of drug treatments. There is now substantial evidence for the diagnostic and prognostic value of long noncoding RNAs (lncRNAs). This review briefly discusses recent findings on the roles and mechanisms of action of lncRNAs in the responses to therapy in non-small cell lung cancer.
Collapse
Affiliation(s)
- Wenjuan Liu
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province 250117, China
| | - Bingli Zuo
- Human Resources Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province 250117, China
| | - Wenting Liu
- Department of Neurology, Weifang People's Hospital, Weifang, Shandong Province 261041, China
| | - Yanfei Huo
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province 250117, China
| | - Nasha Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province 250117, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China.
| | - Ming Yang
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province 250117, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China.
| |
Collapse
|
|
9
|
Han YC, Shen ZJ, Xiang RL, Lu B, Qian H, Li JY, Xie HZ. Long Noncoding RNA and mRNA Expression Profiles in Rats with LPS-induced Myocardial Dysfunction. Curr Genomics 2023; 23:412-423. [PMID: 37920555 PMCID: PMC10173418 DOI: 10.2174/1389202924666230119160258] [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: 06/02/2022] [Revised: 12/09/2022] [Accepted: 01/09/2023] [Indexed: 01/21/2023] Open
Abstract
Background Sepsis is an uncontrolled systemic inflammatory response. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of sepsis. However, little is known about the roles of lncRNAs in sepsis-induced myocardial dysfunction. Objective We aimed to determine the regulatory mechanism of lncRNAs in sepsis-induced myocardial dysfunction. Methods In this study, we analysed the lncRNA and mRNA expression profiles using microarray analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction network, and gene set enrichment analysis were used to evaluate the data. We also constructed coding and noncoding coexpression and competing endogenous RNA networks to investigate the mechanisms. Results In vivo lipopolysaccharide -induced sepsis rat model was established. A total of 387 lncRNAs and 1,952 mRNAs were identified as significantly changed in the left ventricle. Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs showed that the upregulated genes were mainly enriched in the "complement and coagulation cascade pathway" and "immune-related biological processes" terms. Eight significantly changed lncRNAs detected by RT-qPCR may be responsible for these processes. A competing endogenous RNA network was generated, and the results indicated that eight lncRNAs were related to the "calcium ion binding" process. Conclusion These results demonstrate that crosstalk between lncRNAs and mRNAs may play important roles in the development of sepsis-induced myocardial dysfunction.
Collapse
Affiliation(s)
- Ye-Chen Han
- Department of Cardiology, Peking Union Medical College Hospital, No. 1 North Street, Dongdan, Beijing, 100032, China
| | - Zhu-Jun Shen
- Department of Cardiology, Peking Union Medical College Hospital, No. 1 North Street, Dongdan, Beijing, 100032, China
| | - Ruo-Lan Xiang
- School of Basic Medical Sciences, Peking University, Beijing, China
| | - Bo Lu
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Hao Qian
- Department of Cardiology, Peking Union Medical College Hospital, No. 1 North Street, Dongdan, Beijing, 100032, China
| | - Jing-Yi Li
- Department of Cardiology, Peking Union Medical College Hospital, No. 1 North Street, Dongdan, Beijing, 100032, China
| | - Hong-Zhi Xie
- Department of Cardiology, Peking Union Medical College Hospital, No. 1 North Street, Dongdan, Beijing, 100032, China
| |
Collapse
|
|
10
|
Xu JL, Xu Q, Wang YL, Xu D, Xu WX, Zhang HD, Wang DD, Tang JH. Glucose metabolism and lncRNAs in breast cancer: Sworn friend. Cancer Med 2023; 12:5137-5149. [PMID: 36426411 PMCID: PMC9972110 DOI: 10.1002/cam4.5265] [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: 04/21/2022] [Revised: 08/11/2022] [Accepted: 08/26/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Glucose metabolism disorder is a common feature in cancer. Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non-coding RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism-related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer. METHODS 1222 RNA-seq were extracted from the TCGA database, and 74 glucose metabolism-related genes were loaded from the GSEA website. Then, 7 glucose metabolism-related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that high-risk patients predict a poor clinical outcome with high reliability (P=2.838×10-6). Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle-related pathways were significantly enriched in a high-risk group. RESULTS Our results showed that glucose metabolism-related lncRNAs can affect breast cancer progression. 7 glucose metabolism-related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high-risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis. CONCLUSION 7 glucose metabolism-related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple-negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets.
Collapse
Affiliation(s)
- Jia-Lin Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.,The First Clinical School of Nanjing Medical University, Nanjing, P.R. China
| | - Qi Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.,The First Clinical School of Nanjing Medical University, Nanjing, P.R. China
| | - Ya-Lin Wang
- School of Clinical Medicine, Xuzhou Medical University, Xuzhou, P.R. China
| | - Di Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.,The First Clinical School of Nanjing Medical University, Nanjing, P.R. China
| | - Wen-Xiu Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - He-Da Zhang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Dan-Dan Wang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Jin-Hai Tang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| |
Collapse
|
|
11
|
Roohinejad Z, Bahramian S, Shamsabadi FT, Sahebi R, Amini A, Sabour D, Shafiee M. Upregulation of the c-MYC oncogene and adjacent long noncoding RNAs PVT1 and CCAT1 in esophageal squamous cell carcinoma. BMC Cancer 2023; 23:34. [PMID: 36624401 PMCID: PMC9830801 DOI: 10.1186/s12885-022-10464-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 12/20/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND All cell types express long non-coding RNAs (lncRNAs), which have the potential to play a role in carcinogenesis by altering the levels of their expression. Squamous cell carcinoma of the esophagus (ESCC) is a deadly disease with a poor prognosis and a high frequency of lymphatic metastases. Understanding the functional role and signaling pathways of two neighboring lncRNAs, CCAT1 and PVT1, in this oncogene's pathogenesis may help us determine ESCC. Furthermore, it is still unclear whether these lncRNAs are linked to the clinicopathological characteristics of patients with ESCC. METHODS For this study, we used biopsy from the Imam Khomeini Cancer Institute's tumor bank in Tehran, Iran to obtain 40 ESCC tumor samples and their normal margin counterparts. The expression levels of the CCAT1, PVT1, and c-MYC genes were assessed using quantitative Real-Time RT-PCR. Additionally, demographic data and clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node, and metastasis, were taken into consideration. Graphpad prism version 8 was used for bioinformatics analyses. RESULTS Comparing ESCC tissues to non-tumor tissues, we found significant upregulation of PVT1, CCAT1, and c-MYC. Patients with ESCC who had increased PVT1 expression also had higher rates of advanced stage and lymph node metastasis, whereas increased CCAT1 expression was only linked to advanced stage and wasn't associated with lymph node metastasis. In predicting ESCC, CCAT1 (p < 0.05) was found to be an important factor. Overall survival was reduced by c-MYC and PVT1 overexpression (p < 0.001), according to Kaplan-Meier analysis. PVT1, CCAT1, and c-MYC were found to interact with 23 miRNAs with high and medium score classes, as shown in a bioinformatics study. We summarized the experimentally proven interactions between c-MYC, PVT1, and CCAT1 and other miRNAs, lncRNAs, and proteins. CONCLUSION This is the first report that CCAT1, PVT1 and c-MYC have been found to be up-regulated simultaneously in ESCC. It is possible that these genes may be involved in ESCC as a result of these findings. Therefore, as consequence, more research is needed to determine whether or not these lncRNAs play an oncogenic role in ESCC development and progression, as well as the regulatory mechanisms that control them.
Collapse
Affiliation(s)
- Zahra Roohinejad
- Genetic Department, University of Medical Sciences, Ganjafrooz Street, Babol, Mazandaran, Iran
| | - Shabbou Bahramian
- grid.411747.00000 0004 0418 0096Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Tash Shamsabadi
- grid.411747.00000 0004 0418 0096Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Reza Sahebi
- grid.411583.a0000 0001 2198 6209Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolfazl Amini
- grid.411747.00000 0004 0418 0096Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Davood Sabour
- Genetic Department, University of Medical Sciences, Ganjafrooz Street, Babol, Mazandaran, Iran
| | - Mohammad Shafiee
- grid.411747.00000 0004 0418 0096Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| |
Collapse
|
|
12
|
Oliveira AI, Pinho C, Vieira FQ, Silva R, Cruz A. Taraxacum spp. in vitro and in vivo anticancer activity – a review. J Herb Med 2022. [DOI: 10.1016/j.hermed.2022.100612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
|
|
13
|
Kong W, Yin G, Zheng S, Liu X, Zhu A, Yu P, Zhang J, Shan Y, Ying R, Jin H. Long noncoding RNA (lncRNA) HOTAIR: Pathogenic roles and therapeutic opportunities in gastric cancer. Genes Dis 2022; 9:1269-1280. [PMID: 35873034 PMCID: PMC9293693 DOI: 10.1016/j.gendis.2021.07.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 06/21/2021] [Accepted: 07/06/2021] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer is one of the first malignant cancers in the world and a large number of people die every year due to this disease. Many genetic and epigenetic risk factors have been identified that play a major role in gastric cancer. HOTAIR is an effective epigenetic agent known as long noncoding RNA (lncRNA). HOTAIR has been described to have biological functions in biochemical and cellular processes through interactions with many factors, leading to genomic stability, proliferation, survival, invasion, migration, metastasis, and drug resistance. In the present article, we reviewed the prognostic value of the molecular mechanisms underlying the HOTAIR regulation and its function in the development of Gastric Cancer, whereas elucidation of HOTAIR–protein and HOTAIR–DNA interactions can be helpful in the identification of cancer processes, leading to the development of potential therapeutic strategies.
Collapse
Affiliation(s)
- Wencheng Kong
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Guang Yin
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Sixin Zheng
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Xinchun Liu
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Akao Zhu
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Panpan Yu
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Jian Zhang
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Yuqiang Shan
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Rongchao Ying
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Huicheng Jin
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| |
Collapse
|
|
14
|
Abd El Gayed EM, Abo Shady HM, Elhelbawy M, El Deen Arafat ES. Study the relationship between long non-coding RNA (CCAT1) expression and CDK4 expression levels in Egyptian patients with preeclampsia. Biochem Biophys Rep 2022; 31:101294. [PMID: 35733554 PMCID: PMC9207606 DOI: 10.1016/j.bbrep.2022.101294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/19/2022] [Accepted: 05/31/2022] [Indexed: 11/23/2022] Open
Abstract
Background Maternal and perinatal mortality is caused by a variety of factors, including preeclampsia. PE's onset and progression may be influenced by lncRNAs. The effect of long non-coding RNA (lncRNA) Colon cancer-associated transcription factor 1 (CCAT1) expression in the placenta of preeclampsia patients on preeclampsia progression was the focus of this investigation. Objectives The aim of the current study is to check if the levels of expression of Colon cancer-associated transcription factor 1 (CCAT1) and Cyclin-dependent protein kinase 4 (CDK4) are associated with preeclampsia vulnerability and biogenesis. Subjects and methods: This work included the participation of 160 people. Eighty of the patients had preeclampsia. The control group included 80 normal pregnant women. The two groups were almost of the same age. A thorough clinical examination was performed in all groups (including taking a detailed history, concentrating on parity, age and previous background of diabetes or hypertension). The expression levels of CCAT1 and CDK4 in placental tissue were determined using a real-time q PCR technique. Results Expression levels of CCAT1 and CDK4 differed significantly between the study groups. preeclamptic patients having the highest level of CCAT1in comparison with control group, However, preeclamptic patients having lower level of CDK4 than controls. There was a strong negative association between CDK4 expression level and DBP, SBP, creatinine, urea and CCAT1 level of expression in the preeclamptic group, whereas there was a positive correlation between CCAT1 level of expression and DBP, SBP, urea and creatinine in patients group. Conclusion Based on the findings of this study, it is possible that CCAT1 and CDK4 expression levels could be used to aid in the diagnosis and biogenesis of preeclampsia.
Collapse
Affiliation(s)
- Eman Masoud Abd El Gayed
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Egypt
| | - Heba Maged Abo Shady
- Department of Gynecology & Obstetrics Department, Faculty of Medicine, Menoufia University, Egypt
| | - Mohammed Elhelbawy
- Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Egypt
| | - Eman S. El Deen Arafat
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Egypt
| |
Collapse
|
|
15
|
Yang F, Peng ZX, Ji WD, Yu JD, Qian C, Liu JD, Fang GE. LncRNA CCAT1 Upregulates ATG5 to Enhance Autophagy and Promote Gastric Cancer Development by Absorbing miR-140-3p. Dig Dis Sci 2022; 67:3725-3741. [PMID: 34417924 DOI: 10.1007/s10620-021-07187-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/20/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Long noncoding RNA colon cancer-associated transcript 1 (LncRNA CCAT1) is highly expressed in gastric cancer tissues and plays a role in autophagy. However, the underlying mechanism still needs to be further clarified. OBJECTIVE To study the role of LncRNA CCAT1 in regulating autophagy of gastric cancer cells, analyze its downstream targets, and elucidate the mechanism. METHODS qPCR detected the expression of LncRNA CCAT1 in gastric cancer cells. The proliferation, migration, and invasion ability of LncRNA CCAT1 and the expression level of autophagy-related proteins in gastric cancer cells were detected. Bioinformatics method predicted the downstream targets of LncRNA CCAT1, and they were verified by dual-luciferase assay. The relationship between LncRNA CCAT1, miR-140, and ATG5 was verified by co-transfection, and the expression levels of ATG5 and ATG5-ATG12 complex proteins were detected. Finally, the role of LncRNA CCAT1 in vivo was confirmed by gastric cancer transplantation model. RESULTS LncRNA CCAT1 was highly expressed in gastric cancer cells. LncRNA CCAT1 can promote the proliferation, migration, invasion, and autophagy activity of gastric cancer cells. LncRNA CCAT1 can bind to miR-140-3p and regulate its expression, while miR-140-3p further regulates the expression of ATG5. Overexpression of LncRNA CCAT1 can promote tumor growth in nude mice. After LncRNA CCAT1 silencing, the positive expression rate of ATG5 in nude mice was low. CONCLUSION LncRNA CCAT1 may inhibit the expression of miR-140-3p by sponge adsorption, thus weakening its inhibitory effect on ATG5. Eventually, gastric cancer cells were more prone to autophagy under the pressure of stress.
Collapse
Affiliation(s)
- Feng Yang
- Department of General Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 201805, People's Republic of China
| | - Zhang-Xiao Peng
- Molecular Tumor Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 201805, People's Republic of China
| | - Wei-Dan Ji
- Molecular Tumor Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 201805, People's Republic of China
| | - Ju-Dian Yu
- Department of General Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 201805, People's Republic of China
| | - Chen Qian
- Department of General Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 201805, People's Republic of China
| | - Jian-Dong Liu
- Department of General Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 201805, People's Republic of China
| | - Guo-En Fang
- Department of General Surgery, Changhai Hospital, Second Military Medical University, 68 Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China.
| |
Collapse
|
|
16
|
Ferrer JLM, Garcia RL. Antioxidant Systems, lncRNAs, and Tunneling Nanotubes in Cell Death Rescue from Cigarette Smoke Exposure. Cells 2022; 11:2277. [PMID: 35892574 PMCID: PMC9330437 DOI: 10.3390/cells11152277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/17/2022] [Accepted: 07/19/2022] [Indexed: 12/10/2022] Open
Abstract
Cigarette smoke is a rich source of carcinogens and reactive oxygen species (ROS) that can damage macromolecules including DNA. Repair systems can restore DNA integrity. Depending on the duration or intensity of stress signals, cells may utilize various survival and adaptive mechanisms. ROS levels are kept in check through redundant detoxification processes controlled largely by antioxidant systems. This review covers and expands on the mechanisms available to cigarette smoke-exposed cancer cells for restoring the redox balance. These include multiple layers of transcriptional control, each of which is posited to be activated upon reaching a particular stress threshold, among them the NRF2 pathway, the AP-1 and NF-kB pathways, and, finally, TP53, which triggers apoptosis if extreme toxicity is reached. The review also discusses long noncoding RNAs, which have been implicated recently in regulating oxidative stress-with roles in ROS detoxification, the inflammatory response, oxidative stress-induced apoptosis, and mitochondrial oxidative phosphorylation. Lastly, the emerging roles of tunneling nanotubes in providing additional mechanisms for metabolic rescue and the regulation of redox imbalance are considered, further highlighting the expanded redox reset arsenal available to cells.
Collapse
Affiliation(s)
| | - Reynaldo L. Garcia
- Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Quezon City 1101, Philippines;
| |
Collapse
|
|
17
|
Najafi S, Khatami SH, Khorsand M, Jamali Z, Shabaninejad Z, Moazamfard M, Majidpoor J, Aghaei Zarch SM, Movahedpour A. Long non-coding RNAs (lncRNAs); roles in tumorigenesis and potentials as biomarkers in cancer diagnosis. Exp Cell Res 2022; 418:113294. [PMID: 35870535 DOI: 10.1016/j.yexcr.2022.113294] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/11/2022] [Accepted: 07/16/2022] [Indexed: 12/15/2022]
Abstract
New research has indicated that long non-coding RNAs (lncRNAs) play critical roles in a broad range of biological processes, including the pathogenesis of many complex human diseases, including cancer. The detailed regulation mechanisms of many lncRNAs in cancer initiation and progression have yet to be discovered, even though a few of lncRNAs' functions in cancer have been characterized. In the present study, we summarize recent advances in the mechanisms and functions of lncRNAs in cancer. We focused on the roles of newly-identified lncRNAs as oncogenes and tumor suppressors, as well as the potential pathways these molecules could play. The paper also discusses their potential uses as biomarkers for the diagnosis and prognosis of cancer.
Collapse
Affiliation(s)
- Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Seyyed Hossein Khatami
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marjan Khorsand
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Jamali
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Shabaninejad
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Seyed Mohsen Aghaei Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | |
Collapse
|
|
18
|
Ji Y, Yang Y, Yin Z. Polymorphisms in lncRNA CCAT1 on the susceptibility of lung cancer in a Chinese northeast population: A case-control study. Cancer Med 2022; 12:500-512. [PMID: 35650713 PMCID: PMC9844612 DOI: 10.1002/cam4.4902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 05/04/2022] [Accepted: 05/15/2022] [Indexed: 02/06/2023] Open
Abstract
OBJECT To explore the association of rs1948915, rs7013433 in long noncoding RNA (lncRNA) CCAT1 and rs6983267 in MYC enhancer region with the risk of lung cancer in a Chinese northeast population, a case-control study was conducted. METHODS The hospital-based case-control study contained 669 lung cancer patients and 697 healthy controls. Taqman® Probe allele resolution was used for genotyping. The differences between the case-control groups were analyzed using Student t-test and chi-square test. Logistic regression analysis was used to assess the relationship between the genotypes and the risk of lung cancer. Cross-generation analysis was used to explore the relationship between gene-environment interaction and lung cancer. RESULTS There was no association between the three selected single-nucleotide polymorphisms (SNPs) and the susceptibility of lung cancer. Rs1948915 CT was correlated with lung adenocarcinoma. In female stratification, rs1948915 CT/CC was associated with a decreased susceptibility of lung cancer significantly. Additionally, the additive and multiplicative interaction models showed that there was no interaction between the three selected SNPs and smoking status in lung cancer. CONCLUSIONS There may be an association between lung adenocarcinoma and rs1948915 polymorphism in the Chinese northeast population, while rs7013433 and rs6983267 might have no association. There was no interaction between the three selected SNPs and smoking status.
Collapse
Affiliation(s)
- Yangtao Ji
- Department of Laboratory Medicine, National Clinical Research Center for Laboratory MedicineThe First Affiliated Hospital of China Medical UniversityShenyangLiaoningPeople's Republic of China
| | - Yue Yang
- Department of Laboratory MedicineThe First Affiliated Hospital of China Medical UniversityShenyangLiaoningPeople's Republic of China
| | - Zhihua Yin
- Department of EpidemiologySchool of Public Health, China Medical UniversityShenyangLiaoningPeople's Republic of China
| |
Collapse
|
|
19
|
Soltani R, Amini M, Mazaheri Moghaddam M, Jebelli A, Ahmadiyan S, Bidar N, Baradaran B, MotieGhader H, Asadi M, Mokhtarzadeh A. LncRNA DLGAP1-AS2 overexpression associates with gastric tumorigenesis: a promising diagnostic and therapeutic target. Mol Biol Rep 2022; 49:6817-6826. [PMID: 34981339 DOI: 10.1007/s11033-021-07038-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 11/29/2021] [Indexed: 01/10/2023]
Abstract
BACKGROUND Aberrant expression of long noncoding RNAs (lncRNAs) is associated with the progression of human cancers, including gastric cancer (GC). The function of lncRNA DLGAP1-AS2, as a promising oncogene, has been identified in several human cancers. Therefore, this study was aimed to explore the association of DLGAP1-AS2 with gastric tumorigenesis, as well. METHODS AND RESULTS The expression level of DLGAP1-AS2 was initially pre-evaluated in GC datasets from Gene Expression Omnibus (GEO). Moreover, qRT-PCR experiment was performed on 25 GC and 25 adjacent normal tissue samples. The Cancer Genome Atlas (TCGA) data were also analyzed for further validation. Consistent with data obtained from GEO datasets, qRT-PCR results revealed that DLGAP1-AS2 was significantly (p < 0.0032) upregulated in GC specimens compared to normal samples, which was additionally confirmed using TCGA analysis (p < 0.0001). DLGAP1-AS2 expression level was also correlated with age (p = 0.0008), lymphatic and vascular invasion (p = 0.0415) in internal samples as well as poor survival of GC patients (p = 0.00074) in GEO datasets. Also, Gene Ontology analysis illustrated that DLGAP1-AS2 may be involved in the cellular process, including hippo signaling, regulated by YAP1, as its valid downstream target, in GC samples. Moreover, ROC curve analysis showed the high accuracy of the DLGAP1-AS2 expression pattern as a diagnostic biomarker for GC. CONCLUSION Our findings indicated that DLGAP1-AS2 might display oncogenic properties through gastric tumorigenesis and could be suggested as a therapeutic, diagnostic, and prognostic target.
Collapse
Affiliation(s)
- Rogayeh Soltani
- Department of Biology, Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Asiyeh Jebelli
- Department of Biology, Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | - Sahar Ahmadiyan
- Department of Biology, Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | - Negar Bidar
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Habib MotieGhader
- Department of Bioinformatics, Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Milad Asadi
- Department of Basic Oncology, Health Institute of Ege University, Izmir, Turkey
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
|
20
|
Abd El Gayed E, Abd El Gayed A, Arafat E. Study the Relationship between Long Non-Coding RNA (CCAT) Expression and CDK4 Expression Levels in Egyptian Patients with Preeclampsia. SSRN ELECTRONIC JOURNAL 2022. [DOI: 10.2139/ssrn.4014879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
|
|
21
|
Zhang Y, Zhang PS, Rong ZY, Huang C. One stomach, two subtypes of carcinoma-the differences between distal and proximal gastric cancer. Gastroenterol Rep (Oxf) 2021; 9:489-504. [PMID: 34925847 PMCID: PMC8677565 DOI: 10.1093/gastro/goab050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/13/2021] [Accepted: 08/13/2021] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract, posing a significant risk to human health. Over the past 10 years, the pathological characteristics and the prognosis of GC have been determined based on the locations of the tumors that were then classified into two types-proximal and distal GC. This review focuses on the differences in epidemiology, etiology, cell source, pathological characteristics, gene expression, molecular markers, manifestations, treatment, prognosis, and prevention between proximal and distal GC to provide guidance and a basis for clinical diagnosis and treatment.
Collapse
Affiliation(s)
- Yuan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Peng-Shan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Ze-Yin Rong
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| |
Collapse
|
|
22
|
Shafabakhsh R, Arianfar F, Vosough M, Mirzaei HR, Mahjoubin-Tehran M, Khanbabaei H, Kowsari H, Shojaie L, Azar MEF, Hamblin MR, Mirzaei H. Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance. Cancer Gene Ther 2021; 28:1229-1255. [PMID: 33432087 DOI: 10.1038/s41417-020-00272-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/06/2020] [Accepted: 11/23/2020] [Indexed: 02/07/2023]
Abstract
Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.
Collapse
Affiliation(s)
- Rana Shafabakhsh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Farzaneh Arianfar
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Massoud Vosough
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran
| | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Mahjoubin-Tehran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hashem Khanbabaei
- Medical Physics Department, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hamed Kowsari
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Layla Shojaie
- Research Center for Liver Diseases, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| |
Collapse
|
|
23
|
Deng Y, Li J, Zhou M, Liang Z, Zhao L. c-Myc affects hedgehog pathway via KCNQ1OT1/RAC1: A new mechanism for regulating HSC proliferation and epithelial-mesenchymal transition. Dig Liver Dis 2021; 53:1458-1467. [PMID: 33451909 DOI: 10.1016/j.dld.2020.11.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/24/2020] [Accepted: 11/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND This study aimed to probe into the potential mechanism of KCNQ1OT1 in liver fibrosis. METHODS The pathological changes in liver tissues were observed by Masson and hematoxylin-eosin (HE) staining. The proliferation or cell cycle of hepatic stellate cells (HSCs) was analyzed by MTT or flow cytometry. The expressions of epithelial markers E-cadherin, interstitial markers Snail and Vimentin, and hedgehog signaling pathway-related molecules Hhip, Shh, and Gli2 were detected by Western blot. The interaction or binding of c-Myc with the KCNQ1OT1 promoter was analyzed by dual-luciferase reporter gene or Chromatin immunoprecipitation (ChIP)-qPCR, and the interaction between KCNQ1OT1 and RAC1 was assessed by RNA immunoprecipitation and RNA pull-down. Moreover, the stability of RAC1 protein was detected by cycloheximide-chase and ubiquitination. RESULTS c-Myc and KCNQ1OT1 were up-regulated in liver fibrosis tissues and cells. After the interference with c-Myc in primary-1-Day HSCs, the down-regulated KCNQ1OT1 restrained HSC proliferation and EMT by down-regulating RAC1 expression and restraining the hedgehog pathway. CONCLUSION Our results indicated that the interference with c-Myc down-regulated RAC1 expression and restrained the hedgehog pathway by down-regulating KCNQ1OT1, thus restraining HSC proliferation and EMT in liver fibrosis.
Collapse
Affiliation(s)
- Yilei Deng
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
| | - Jian Li
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Menghao Zhou
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Zhiwei Liang
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Longshuan Zhao
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| |
Collapse
|
|
24
|
Eshghifar N, Rouhollah F, Barikrow N, Pouresmaeili F, Taheri M. The role of long noncoding RNAs in patients with Luminal A invasive breast ductal carcinoma. Pathol Res Pract 2021; 227:153645. [PMID: 34678601 DOI: 10.1016/j.prp.2021.153645] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/28/2021] [Accepted: 09/30/2021] [Indexed: 12/25/2022]
Abstract
Breast cancer is the most common form of cancer in women around the world. The molecular mechanisms of this heterogeneous disease have been extensively investigated; but yet; It requires a lot of sensitive and specific markers for prognosis and early detection approaches. Non-protein coding RNAs known as lncRNAs have been reported in tumorigenic involvement so they can be used for therapeutic purposes. In the present study, the expression levels of CCAT1, PDCD4, PDCD4-AS1, and MEG3 LncRNA in adjacent tumor and breast tissue in 88 Iranian patients were evaluated by quantitative real-time PCR. CCAT1 was significantly expressed and PDCD4-AS1 decreased in tumor samples, PDCD4 and PDCD4-AS1 showed a positive correlation with each other, higher levels of PDCD4-AS1 were associated with better survival, tumor samples showed lower levels of PDCD4 in Showed comparisons with normal tissue. Our findings suggest that lncRNAs play an important role in controlling gene expression after transcription of major tumor suppressors or carcinogenic genes, leading to the development of triple-negative breast cancer (TNBC). In conclusion, this study investigated the prognostic role of lncRNA in breast cancer patients.
Collapse
Affiliation(s)
- Nahal Eshghifar
- Department of Cellular and Molecular Sciences, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Fatemeh Rouhollah
- Department of Cellular and Molecular Sciences, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Nooshin Barikrow
- Department of Cellular and Molecular Sciences, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Farkhondeh Pouresmaeili
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
25
|
Tseng HH, Chen YZ, Chou NH, Chen YC, Wu CC, Liu LF, Yang YF, Yeh CY, Kung ML, Tu YT, Tsai KW. Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis. MOLECULAR THERAPY-ONCOLYTICS 2021; 22:180-194. [PMID: 34514098 PMCID: PMC8416970 DOI: 10.1016/j.omto.2021.08.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 08/13/2021] [Indexed: 12/30/2022]
Abstract
Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.
Collapse
Affiliation(s)
- Hui-Hwa Tseng
- Division of Anatomic Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23124, Taiwan
| | - You-Zuo Chen
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.,Department of Biological Science and Technology, I-Shou University, Kaohsiung 82445, Taiwan
| | - Nan-Hua Chou
- Department of Surgery Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
| | - Yen-Chih Chen
- Division of Gastrointestinal Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical of Foundation, New Taipei City 23124, Taiwan
| | - Chao-Chuan Wu
- Division of Gastrointestinal Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical of Foundation, New Taipei City 23124, Taiwan
| | - Li-Feng Liu
- Department of Biological Science and Technology, I-Shou University, Kaohsiung 82445, Taiwan
| | - Yi-Fang Yang
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
| | - Chung-Yu Yeh
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
| | - Mei-Lang Kung
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
| | - Ya-Ting Tu
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23124, Taiwan
| | - Kuo-Wang Tsai
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23124, Taiwan
| |
Collapse
|
|
26
|
Chu Y, Wang X, Yu N, Li Y, Kan J. Long non‑coding RNA FGD5‑AS1/microRNA‑133a‑3p upregulates aquaporin 1 to decrease the inflammatory response in LPS‑induced sepsis. Mol Med Rep 2021; 24:784. [PMID: 34498707 DOI: 10.3892/mmr.2021.12424] [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: 12/17/2020] [Accepted: 04/19/2021] [Indexed: 11/06/2022] Open
Abstract
Sepsis is a systemic inflammatory response syndrome caused by infections. The present study aimed to investigate the potential mechanism of FGD5‑AS1 in sepsis and lipopolysaccharide (LPS)‑induced inflammatory response. An animal model of sepsis was constructed. LPS was used to induce mice HL‑1 cardiomyocytes to construct a cell model. The association between FGD5‑AS1 and miR‑133a‑3p was investigated through animal and cell models. FGD5‑AS1 overexpression was used to analyze the effect of FGD5‑AS1 on inflammatory reaction. Tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 levels were detected by enzyme‑linked immunosorbent assay and reverse transcription‑quantitative polymerase chain reaction. The interaction of FGD5‑AS1, miR‑133a‑3p and aquaporin 1 (AQP1) was detected by dual‑luciferase reporter assay and microRNA (miRNA/miR) pull‑down assay. Compared with the control group, the expression of FGD5‑AS1 was decreased and the expression of miR‑133a‑3p was increased in the sepsis group. FGD5‑AS1 overexpression increased LPS‑induced expression of FGD5‑AS1 and AQP1, decreased the expression of miR‑133a‑3p, and inhibited the expression of the inflammatory cytokines, TNF‑α, IL‑6 and IL‑1β. Dual‑luciferase reporter and miRNA pull‑down assays confirmed the interaction of FGD5‑AS1, miR‑133a‑3p and AQP1. These results indicated that FGD5‑AS1 is the competitive endogenous RNA of miR‑133a‑3p on AQP1, and thus FGD5‑AS1 overexpression may be able to inhibit the inflammatory response in sepsis.
Collapse
Affiliation(s)
- Yuru Chu
- Intensive Care Unit, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China
| | - Xu Wang
- Acupuncture Department, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China
| | - Naihao Yu
- Intensive Care Unit, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China
| | - Yali Li
- Intensive Care Unit, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China
| | - Jianying Kan
- Intensive Care Unit, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China
| |
Collapse
|
|
27
|
The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer. Biomedicines 2021; 9:biomedicines9080921. [PMID: 34440124 PMCID: PMC8389562 DOI: 10.3390/biomedicines9080921] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/25/2021] [Accepted: 07/28/2021] [Indexed: 01/17/2023] Open
Abstract
Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types.
Collapse
|
|
28
|
Olesiński T, Lutkowska A, Balcerek A, Sowińska A, Piotrowski P, Trzeciak T, Maj T, Hevelke P, Jagodziński PP. Long noncoding RNA CCAT1 rs67085638 SNP contribution to the progression of gastric cancer in a Polish population. Sci Rep 2021; 11:15369. [PMID: 34321511 PMCID: PMC8319342 DOI: 10.1038/s41598-021-94576-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 07/07/2021] [Indexed: 01/17/2023] Open
Abstract
The role of the long noncoding RNA CCAT1 NC_000008.10:g.128220661C > T (rs67085638) in the development of colon cancer has been reported. Therefore, we assessed the prevalence of rs67085638 in patients with gastric cancer (GC). We also evaluated the effect of rs67085638 on B-cell-specific Moloney leukaemia virus insertion site 1 (BMI1) transcripts in primary GC and counterpart histopathologically confirmed disease-free margin tissue. Using high-resolution melting analysis, we evaluated rs67085638 frequency in patients with the GC genotype (n = 214) and controls (n = 502) in a Polish Caucasian population. qRT-PCR was used to determine BMI1 transcripts. We observed the trend of rs67085638 association in all patients with GC (ptrend = 0.028), a strong risk of the GC genotype in male (ptrend = 0.035) but not female (ptrend = 0.747) patients, and the association with non-cardia GC (ptrend = 0.041), tumour stages T3 (ptrend = 0.014) and T4 (ptrend = 0.032), differentiation grading G3 (ptrend = 0.009), lymph node metastasis stage N3 (ptrend = 0.0005) and metastasis stage M0 (ptrend = 0.027). We found that significantly increased BMI1 transcripts were associated with the primary GC genotype classified as grade G3 (p = 0.011) and as lymph node metastasis N3 (p = 0.010) and counterpart marginal tissues (p = 0.026, p = 0.040, respectively) from carriers of the T/T versus C/C genotypes. rs67085638 may contribute to increased BMI1 transcripts and the progression and rapid growth of GC.
Collapse
Affiliation(s)
- Tomasz Olesiński
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Anna Lutkowska
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781, Poznan, Poland
| | - Adam Balcerek
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781, Poznan, Poland
| | - Anna Sowińska
- Department of Computer Science and Statistics, Poznań University of Medical Sciences, Poznan, Poland
| | - P Piotrowski
- Molecular Biology Department, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
| | - Tomasz Trzeciak
- Department of Orthopedics and Traumatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Tomasz Maj
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Piotr Hevelke
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Pawel P Jagodziński
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781, Poznan, Poland.
| |
Collapse
|
|
29
|
Kang B, Qiu C, Zhang Y. The Effect of lncRNA SNHG3 Overexpression on Lung Adenocarcinoma by Regulating the Expression of miR-890. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:1643788. [PMID: 34306585 PMCID: PMC8285187 DOI: 10.1155/2021/1643788] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/25/2021] [Indexed: 12/17/2022]
Abstract
The lncRNA small nucleolar host gene 3 (SNHG3) was discovered to play an important role in the occurrence and development of lung adenocarcinoma (LUAD). However, the underlying molecular mechanism of SNHG3 in LUAD remains unclear. In the present study, SNHG3 expression levels in LUAD tissues and cell lines were analyzed using reverse transcription-quantitative PCR. The effects of SNHG3 on the proliferation, apoptosis, migration, and invasion of LUAD cells were determined using Cell Counting Kit-8, colony formation, flow cytometry, wound healing, and Transwell chamber assays, respectively. The specific underlying mechanism of SNHG3 in LUAD was investigated using bioinformatics analysis and a dual luciferase reporter assay. The results revealed that SNHG3 expression levels were downregulated in LUAD tissues and cell lines. Functionally, SNHG3 overexpression suppressed the proliferation, migration, and invasion of LUAD cells, while promoting apoptosis. Mechanistically, microRNA- (miR-) 890 was identified as a potential target of SNHG3, and its expression was negatively regulated by SNHG3. Notably, SNHG3 was found to promote LUAD progression by targeting miR-890. In conclusion, the findings of the present study revealed that lncRNA SNHG3 promoted the occurrence and progression of LUAD by regulating miR-890 expression.
Collapse
Affiliation(s)
- Baojie Kang
- Department of Respiratory, Weifang Yidu Central Hospital, Weifang City, Shandong, China
| | - Caihong Qiu
- Department of Respiratory, Weifang Yidu Central Hospital, Weifang City, Shandong, China
| | - Ying Zhang
- Department of ICU, Zibo Central Hospital, Zibo City, Shandong, China
| |
Collapse
|
|
30
|
Xiao K, Dong Z, Wang D, Liu M, Ding J, Chen W, Shang Z, Yue C, Zhang Y. Clinical value of lncRNA CCAT1 in serum extracellular vesicles as a potential biomarker for gastric cancer. Oncol Lett 2021; 21:447. [PMID: 33868485 PMCID: PMC8045156 DOI: 10.3892/ol.2021.12708] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 03/03/2021] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) in extracellular vesicles (EVs) are considered to be novel non-invasive biomarkers for gastric cancer (GC). lncRNA colon cancer-associated transcript 1 (CCAT1) is aberrantly expressed in certain types of cancer. However, the role of EV lncRNA CCAT1 in patients with GC remains unclear. The current study aimed to assess the expression levels of lncRNA CCAT1 in the serum EVs of patients with GC and evaluate its potential clinical value. EVs were isolated from serum using a commercial kit and ultracentrifugation, and were identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Serum EV lncRNA CCAT1 levels in patients with GC, chronic gastritis or atypical hyperplasia and healthy control subjects were detected by reverse transcription-quantitative PCR. Additionally, lncRNA CCAT1 was detected in GC and adjacent non-cancerous tissue samples. Serum EVs were successfully isolated and identified in all patients. The results revealed that serum EV lncRNA CCAT1 levels in patients with GC were significantly higher compared with those in healthy controls, patients with chronic gastritis or atypical hyperplasia (all P<0.05). Additionally, EV lncRNA CCAT1 expression levels were significantly different among various groups based on the depth of invasion, distant metastasis and the Tumor-Node-Metastasis stage. The area under the curve (AUC) value of EV lncRNA CCAT1 was 0.890 [95% confidence interval (CI), 0.826–0.937] with 79.6% sensitivity and 92.6% specificity. The combination of EV lncRNA CCAT1 and carcinoembryonic antibody produced an AUC value of 0.910 (95% CI, 0.849–0.951) with the sensitivity and specificity of 80.5 and 92.6%, respectively. In addition, lncRNA CCAT1 was determined to be stable in serum EVs. The expression levels of lncRNA CCAT1 in GC tissue were positively correlated with those in serum EVs, and high levels of lncRNA CCAT1 were associated with a low disease-free survival rate in patients with GC. The results of the present study demonstrated that serum EV lncRNA CCAT1 levels were upregulated in patients with GC compared with those healthy subjects and patients with other illnesses, and may therefore be used as a novel biomarker for this type of cancer.
Collapse
Affiliation(s)
- Ke Xiao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Zhaogang Dong
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Ding Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Min Liu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Juan Ding
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Wendan Chen
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Ziqi Shang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Congbo Yue
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| |
Collapse
|
|
31
|
Pu J, Wu X, Wu Y, Shao Z, Luo C, Tang Q, Wang J, Wei H, Lu Y. Anti-oncogenic effects of SOX2 silencing on hepatocellular carcinoma achieved by upregulating miR-222-5p-dependent CYLD via the long noncoding RNA CCAT1. Aging (Albany NY) 2021; 13:12207-12223. [PMID: 33952719 PMCID: PMC8109057 DOI: 10.18632/aging.103797] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 05/01/2020] [Indexed: 01/17/2023]
Abstract
In this study, we determined the involvement of SOX2 and its downstream signaling molecules in hepatocellular carcinoma (HCC) progression. We carried out lentiviral transfection in HepG2 cells to determine the roles of SOX2, CCAT1, EGFR, miR-222-5p, and CYLD in HepG2 cells. We first determined the interaction between SOX2 and CCAT1 and that between miR-222-5p and CYLD and their effect on tumor growth in vivo was analyzed in HCC-xenograft bearing nude mice xenografts. SOX2 and CCAT1 were highly expressed in HCC tissues and HepG2 cells. SOX2 bound to the regulatory site of CCAT1. Silencing of SOX2 or CCAT1 inhibited HepG2 cell proliferation, migration, and invasion as well as decreased the expression of CCAT1 and EGFR. CCAT1 silencing reduced EGFR expression, but EGFR expression was increased in HCC tissues and HepG2 cells, which promoted proliferation, migration, and invasion in vitro. EGFR upregulated miR-222-5p, leading to downregulation of CYLD. miR-222-5p inhibition or CYLD overexpression repressed cell functions in HepG2 cells. SOX2 silencing decreased CCAT1, EGFR, and miR-222-5p expression but increased CYLD expression. Loss of SOX2 also reduced the growth rate of tumor xenografts. In summary, SOX2-mediated HCC progression through an axis involving CCAT1, EGFR, and miR-222-5p upregulation and CYLD downregulation.
Collapse
Affiliation(s)
- Jian Pu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Xianjian Wu
- Graduate College of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Yi Wu
- Graduate College of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Zesheng Shao
- Graduate College of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Chunying Luo
- Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Qianli Tang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Jianchu Wang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Huamei Wei
- Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| | - Yuan Lu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, P.R. China.,Graduate College of Youjiang Medical University for Nationalities, Baise 533000, P.R. China
| |
Collapse
|
|
32
|
Khajehdehi M, Khalaj-Kondori M, Ghasemi T, Jahanghiri B, Damaghi M. Long Noncoding RNAs in Gastrointestinal Cancer: Tumor Suppression Versus Tumor Promotion. Dig Dis Sci 2021; 66:381-397. [PMID: 32185664 DOI: 10.1007/s10620-020-06200-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 03/07/2020] [Indexed: 01/17/2023]
Abstract
Approximately 80% of the human genome harbors biochemical marks of active transcription that its majority transcribes to noncoding RNAs, namely long noncoding RNAs (lncRNAs). LncRNAs are heterogeneous RNA transcripts that regulate critical biological processes such as cell survival and death. They involve in the progression of different cancers by affecting transcriptional and post-transcriptional modifications as well as epigenetic control of numerous tumor suppressors and oncogenes. Recent findings show that aberrant expression of lncRNAs is associated with tumor initiation, progression, invasion, and overall survival of patients with gastrointestinal (GI) cancers. Some lncRNAs play as tumor suppressors in all GI cancers, but others play as tumor promoters. However, some other lncRNAs might function as a tumor suppressor in one GI cancer, but as a tumor promoter in another GI cancer type. This fact highlights possible context dependency of the expression patterns and roles of at least some lncRNAs in GI cancer development and progression. Here, we review the functional relation of lncRNAs involved in the development and progression of GI cancer by focusing on their roles as tumor suppressor and tumor promoter genes.
Collapse
Affiliation(s)
- Mina Khajehdehi
- Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran
| | - Mohammad Khalaj-Kondori
- Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
| | - Tayyebeh Ghasemi
- Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran
| | - Babak Jahanghiri
- Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Mehdi Damaghi
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, 33612, FL, USA
| |
Collapse
|
|
33
|
Pang L, Zhang Q, Wu Y, Yang Q, Zhang J, Liu Y, Li R. Long non-coding RNA CCAT1 promotes non-small cell lung cancer progression by regulating the miR-216a-5p/RAP2B axis. Exp Biol Med (Maywood) 2021; 246:142-152. [PMID: 33023331 PMCID: PMC7871119 DOI: 10.1177/1535370220961013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 09/02/2020] [Indexed: 12/17/2022] Open
Abstract
The long non-coding RNA colon cancer-associated transcript 1 (CCAT1) has been investigated to involve in the progression of non-small cell lung cancer (NSCLC). Thus, this study aims to explore the detailed molecular mechanisms of CCAT1 in NSCLC. The expression of CCAT1, miR-216a-5p, RAP2B, Bax, Bcl-2, and cleaved caspase 3 was detected by qRT-PCR or Western blot. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8, flow cytometry or Transwell assays, respectively. The interaction between miR-216a-5p and CCAT1 or RAP2B was analyzed by luciferase reporter, RNA immunoprecipitation, and pull-down assays. The expression of CCAT1 was elevated in NSCLC, and CCAT1 deletion could inhibit NSCLC cell proliferation, migration, and invasion but induce apoptosis in vitro as well as imped tumor growth in vivo. MiR-216a-5p was confirmed to be a target of CCAT1, and silencing miR-216a-5p could reverse CCAT1 depletion-mediated inhibitory effects on cell tumorigenesis in NSCLC. Besides that, miR-216a-5p was decreased in NSCLC, and miR-216a-5p restoration inhibited cell tumorigenesis by regulating RAP2B, which was verified to be a target of miR-216a-5p. Additionally, co-expression analysis suggested that CCAT1 indirectly regulated RAP2B level by targeting miR-216a-5p in NSCLC cells. Taken together, CCAT1 deletion could inhibit cell progression in NSCLC through miR-216a-5p/RAP2B axis, indicating a novel pathway underlying NSCLC cell progression and providing new potential targets for NSCLC treatment.
Collapse
Affiliation(s)
- Lingling Pang
- Department of Respiratory Medicine, Yantai Yuhuangding Hospital, Yantai 264000, China
| | - Qianqian Zhang
- Department of Respiratory Medicine, Yantai Muping District Chinese Medical Hospital, Yantai 264100, China
| | - Yanmin Wu
- Department of Respiratory Medicine, Xuzhou Central Hospital, Xuzhou 221009, China
| | - Qingru Yang
- Department of Respiratory Medicine, Xuzhou Central Hospital, Xuzhou 221009, China
| | - Jinghao Zhang
- Department of Respiratory Medicine, Xuzhou Central Hospital, Xuzhou 221009, China
| | - Yuanyuan Liu
- Department of Respiratory Medicine, Xuzhou Central Hospital, Xuzhou 221009, China
| | - Ruoran Li
- Department of Respiratory Medicine, Xuzhou Central Hospital, Xuzhou 221009, China
| |
Collapse
|
|
34
|
Xia X, Niu H, Ma Y, Qu B, He M, Yu K, Wang E, Zhang L, Gu J, Liu G. LncRNA CCAT1 Protects Astrocytes Against OGD/R-Induced Damage by Targeting the miR-218/NFAT5-Signaling Axis. Cell Mol Neurobiol 2020; 40:1383-1393. [PMID: 32239388 PMCID: PMC11448959 DOI: 10.1007/s10571-020-00824-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 03/02/2020] [Indexed: 12/19/2022]
Abstract
Spinal cord injury (SCI) is a grievous neurology-related disorder that causes many devastating symptoms. Emerging roles of long non-coding RNAs (lncRNA) have been shown to play critical roles in multiple neurological diseases. This research planned to dig the function and latent molecular mechanisms of the lncRNA CCAT1 on OGD/R-disposed injury in astrocytes. We observed that CCAT1 expression was diminished and miR-218 expression was elevated in astrocytes during OGD/R. Additionally, an abundance of CCAT1 obviously amplified cell viability and restrained OGD/R-triggered apoptosis in astrocytes, as characterized by reduced levels of pro-apoptotic proteins Bax and C-caspase-3, concomitant with elevated level of anti-apoptotic Bcl-2 protein. Furthermore, administration of CCAT1 remarkably mitigated OGD/R injury-induced neuro-inflammatory responses, reflected in a reduction of inflammatory cytokines including TNF-α, IL-1β, and IL-6. In action, CCAT1 served as an endogenous sponge effectively downregulating miR-218 expression by binding directly to it, and a negative regulatory relationship between miR-218 and NFAT5. Mechanistically, introduction of miR-218 reversed the inhibitory effects of CCAT1 on OGD/R-induced apoptosis and inflammation damage, which directly resulted from the inhibition of miR-218 and its targeting of NFAT5. Collectively, our study illuminated a new CCAT1/miR-218/NFAT5 regulatory axis in which CCAT1 served as a competing endogenous RNA by sponging miR-218, effectively upregulating NFAT5 expression, thereby alleviating apoptosis and inflammation damage under OGD/R condition. CCAT1 is, therefore, a putative therapeutic target for SCI, based on the results of this study and the potential application of CCAT1 as a neuroprotective agent.
Collapse
Affiliation(s)
- Xun Xia
- Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu, 610500, Sichuan, People's Republic of China
| | - Hao Niu
- Sichuan Institute of Computer Science, Chengdu, 610041, Sichuan, People's Republic of China
| | - Yuan Ma
- Department of Neurosurgery, General Hospital of Western Theater Command, Chengdu, 610083, Sichuan, People's Republic of China
| | - Bo Qu
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, People's Republic of China
| | - Mingjie He
- Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu, 610500, Sichuan, People's Republic of China
| | - Kai Yu
- Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu, 610500, Sichuan, People's Republic of China
| | - Enren Wang
- Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu, 610500, Sichuan, People's Republic of China
| | - Lie Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu, 610500, Sichuan, People's Republic of China
| | - Jianwen Gu
- Department of Neurosurgery, PLA Strategic Support Force Specialty Medical Center, NO.9 Anxiangbeili, Chaoyang District, Beijing, 100101, People's Republic of China.
| | - Gang Liu
- Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, NO. 278 Baoguang Avenue Middle Section, Xindu District, Chengdu, 610500, Sichuan, People's Republic of China
| |
Collapse
|
|
35
|
Liao C, Guo Y, Gong Y, Huang X, Liao X, Wang X, Ruan G, Gao F. Clinical implications and nomogram prediction of long noncoding RNA FRGCA as diagnostic and prognostic indicators in colon adenocarcinoma. Medicine (Baltimore) 2020; 99:e22806. [PMID: 33126318 PMCID: PMC7598802 DOI: 10.1097/md.0000000000022806] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer, especially colon adenocarcinoma (COAD), is associated with significant morbidity and mortality worldwide. Long noncoding RNA (lncRNA) has been implicated in tumorigenesis. The aim of the present study was to elucidate the potential diagnostic and prognostic values of lncRNA FRGCA in COAD.The data of 438 COAD patients were retrieved for analysis. Diagnostic significance was evaluated using tumor and nontumor tissues. Prognostic significance was evaluated using a Cox proportional regression model. Stratified analysis was performed to identify associations between clinical factors and lncRNA FRGCA expression. A nomogram was constructed using the clinical factors and lncRNA FRGCA for survival prediction. Enrichment analysis identified gene ontologies and metabolic pathways of mRNAs with high Pearson correlation coefficients with lncRNA FRGCA.lncRNA FRGCA was highly expressed in tumor tissues of COAD and demonstrated diagnostic value (area under curve = 0.763, P < .0001). Prognostic significance analysis indicated that lncRNA FRGCA had prognostic value in COAD [adjusted P < .001, hazard ratio (HR) = 0.444, 95% confidence interval (95% CI) = 0.288-0.685] and high expression of lncRNA FRGCA indicated better survival in COAD. A nomogram was evaluated for prediction of survival at 1, 3, and 5 years. Enrichment analysis revealed many mRNAs involved in the structural constituents of the mitochondrial inner membrane and translational termination, protein binding, translation, ribosome, oxidative phosphorylation, and metabolic pathways, especially the nucleoplasm.Differentially expressed in tumor vs nontumor tissues, lncRNA FRGCA had both diagnostic and prognostic implications in COAD, which may be associated with ribosome metabolism, oxidative phosphorylation, and nucleoplasm-related metabolic pathways.
Collapse
Affiliation(s)
- Cun Liao
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Yun Guo
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Yizhen Gong
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Xue Huang
- Department of Gastroenterology, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Xiangkun Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Guotian Ruan
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Feng Gao
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| |
Collapse
|
|
36
|
Luo R, Li L, Hu Y, Xiao F. LncRNA H19
inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting
miR
‐19b to increase
SIRT1
expression. Kaohsiung J Med Sci 2020; 37:101-110. [PMID: 33022863 DOI: 10.1002/kjm2.12302] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 07/17/2020] [Accepted: 08/30/2020] [Indexed: 12/12/2022] Open
Affiliation(s)
- Rong Luo
- Department of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang China
| | - Lan Li
- Department of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang China
| | - Yu‐Xiang Hu
- Department of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang China
| | - Fan Xiao
- Department of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang China
| |
Collapse
|
|
37
|
Zhou H, Feng B, Abudoureyimu M, Lai Y, Lin X, Tian C, Huang G, Chu X, Wang R. The functional role of long non-coding RNAs and their underlying mechanisms in drug resistance of non-small cell lung cancer. Life Sci 2020; 261:118362. [PMID: 32871184 DOI: 10.1016/j.lfs.2020.118362] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/21/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid cancer and the main origin of cancer-related deaths worldwide. Current strategies to treat advanced NSCLC are based on a combined approach of targeted therapy and chemotherapy. But most patients will eventually get resistance to either chemotherapy or targeted therapy, leading to the poor prognosis. The mechanism of NSCLC drug resistance is inconclusive and is affected by multiple factors. Long non-coding RNAs (LncRNAs) are non-coding RNAs (ncRNAs) longer than 200 nucleotides. Recent studies show that lncRNAs are involved in many cellular physiological activities, including drug resistance of NSCLC. It is of great clinical significance to understand the specific mechanisms and the role of lncRNAs in it. CONCLUSIONS Herein, we focus on the functional roles and the underlying mechanisms of lncRNAs in acquired drug resistance of NSCLC. LncRNAs have potential values as novel prognostic biomarkers and even therapeutic targets in the clinical management of NSCLC.
Collapse
Affiliation(s)
- Hao Zhou
- Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, China
| | - Bing Feng
- Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Mubalake Abudoureyimu
- Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Yongting Lai
- Department of Medical Oncology, Nanjing School of Clinical Medicine, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Xinrong Lin
- Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Chuan Tian
- Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Guichun Huang
- Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China.
| | - Xiaoyuan Chu
- Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China; Department of Medical Oncology, Nanjing School of Clinical Medicine, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Rui Wang
- Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, China; Department of Medical Oncology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China.
| |
Collapse
|
|
38
|
Dang S, Malik A, Chen J, Qu J, Yin K, Cui L, Gu M. LncRNA SNHG15 Contributes to Immuno-Escape of Gastric Cancer Through Targeting miR141/PD-L1. Onco Targets Ther 2020; 13:8547-8556. [PMID: 32943878 PMCID: PMC7468375 DOI: 10.2147/ott.s251625] [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: 04/15/2020] [Accepted: 08/01/2020] [Indexed: 01/04/2023] Open
Abstract
Introduction Long non-coding RNAs (lncRNAs) have been demonstrated to participate in many biological processes and severs as important regulators during the progression of gastric cancer. Methods Here, we introduced human lncRNA SNHG15 which was highly expressed in gastric cancer and cells. Interestingly, the expression of SNHG15 was correlated with programmed cell death ligand 1 (PD-L1), which promotes the resistance of gastric cancer cells to immune responses. Meanwhile, SNHG15 downregulation suppressed the expression of PD-L1 and resistance of immune responses. Results Further, our results suggested that SNHG15 acted as a competing endogenous RNA (CeRNA) to sponge miR-141, which was downregulated in gastric cancers and negatively correlated to PD-L1. Conclusion Our results suggested that SNHG15 improved the expression of PD-L1 by inhibiting miR-141, which in turn promoted the resistance of stomach cancer cells to the immune responses.
Collapse
Affiliation(s)
- Shengchun Dang
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China.,Department of General Surgery, Pucheng Hospital, Weinan, Shaanxi Province 715500, People's Republic of China
| | - Abdul Malik
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China
| | - Jixiang Chen
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China
| | - Jianguo Qu
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China
| | - Kai Yin
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China
| | - Lei Cui
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, People's Republic of China
| | - Min Gu
- Department of Oncology, Zhenjiang Hospital of Traditional Chinese and Western Medicine, Zhenjiang, Jiangsu 212001, People's Republic of China
| |
Collapse
|
|
39
|
Alipoor B, Parvar SN, Sabati Z, Ghaedi H, Ghasemi H. An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance. Mol Biol Rep 2020; 47:6357-6374. [PMID: 32743775 DOI: 10.1007/s11033-020-05695-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/26/2020] [Indexed: 12/24/2022]
Abstract
Accumulating evidence has reported that H19 long non-coding RNA (lncRNA) expression level is deregulated in human cancer. It has been also demonstrated that de-regulated levels of H19 could affect cancer biology by various mechanisms including microRNA (miRNA) production (like miR-675), miRNA sponging and epigenetic modifications. Furthermore, lncRNA could act as a potential diagnosis and prognosis biomarkers and also a candidate therapeutic approach for different human cancers. In this narrative review, we shed light on the molecular mechanism of H19 in cancer development and pathogenesis. Moreover, we discussed the expression pattern and diagnostic and therapeutic importance of H19 as a potential biomarker in a range of human malignancies from breast to osteosarcoma cancer.
Collapse
Affiliation(s)
- Behnam Alipoor
- Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Seyedeh Nasrin Parvar
- Department of Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Zolfaghar Sabati
- Student Research Committee, Abadan Faculty of Medical Sciences, Abadan, Iran
| | - Hamid Ghaedi
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Ghasemi
- Department of Clinical Biochemistry, Abadan Faculty of Medical Sciences, Abadan, Iran.
| |
Collapse
|
|
40
|
Long Noncoding RNA HOXD-AS1 Promotes the Proliferation, Migration, and Invasion of Colorectal Cancer via the miR-526b-3p/CCND1 Axis. J Surg Res 2020; 255:525-535. [PMID: 32640404 DOI: 10.1016/j.jss.2020.05.078] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 04/23/2020] [Accepted: 05/24/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies in the world. It has been reported that the abnormal expression of long noncoding RNA HOXD-AS1 promotes the development of CRC, while the mechanism is still unclear. The aim of this study is to investigate the effects of HOXD-AS1 on proliferation, migration, and invasion in CRC and explore the underlying mechanism. METHODS Quantitative real-time polymerase chain reaction was used to detect the expression levels of HOXD-AS1, miR-526b-3p, and cyclin D1 (CCND1) in CRC tissues and cells. Dual-luciferase reporter assay was applied to examine the interaction between miR-526b-3p and HOXD-AS1 or CCND1. In addition, cell proliferation ability was assessed by Cell Counting Kit-8 assay. Cell migration and invasion abilities were determined using transwell assay. Furthermore, Western blot assay was conducted to measure the protein expression of CCND1. RESULTS HOXD-AS1 was highly expressed in CRC, and high expression of HOXD-AS1 was related to the poor prognosis of patients with CRC. MiR-526b-3p could be targeted by HOXD-AS1. Function experiment results revealed that miR-526b-3p inhibitor could reverse the suppressive effect of HOXD-AS1 knockdown on the proliferation, migration, and invasion of CRC cells. Moreover, CCND1 was a target of miR-526b-3p, and its overexpression could reverse the inhibitory effect of miR-526b-3p overexpression on the proliferation, migration, and invasion of CRC cells. In addition, CCND1 overexpression reversed the suppressive effect of HOXD-AS1 knockdown on the proliferation, migration, and invasion of CRC. CONCLUSIONS HOXD-AS1 upregulated the expression of CCND1 to promote the proliferation, migration, and invasion of CRC through targeting miR-526b-3p. This provided a new theoretical basis for clinical anticancer research of CRC.
Collapse
|
|
41
|
Fan J, Kang X, Zhao L, Zheng Y, Yang J, Li D. Long Noncoding RNA CCAT1 Functions as a Competing Endogenous RNA to Upregulate ITGA9 by Sponging MiR-296-3p in Melanoma. Cancer Manag Res 2020; 12:4699-4714. [PMID: 32606961 PMCID: PMC7308122 DOI: 10.2147/cmar.s252635] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/22/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Melanoma is aggressive and lethal melanocytic neoplasm, and its incidence has increased worldwide in recent decades. Accumulating evidence has showed that various long noncoding RNAs (lncRNAs) participated in occurrence of malignant tumors, including melanoma. The present study was designed to investigate function of lncRNA colon cancer-associated transcript-1 (CCAT1) in melanoma. METHODS The expression levels of CCAT1, miR-296-3p and Integrin alpha9 (ITGA9) in melanoma tissues or cells were measured using real-time quantitative polymerase chain reaction (RT-qPCR). The concentrations of glucose and lactate were measured for assessing glycolysis of melanoma cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays were conducted to assess proliferation, apoptosis, and migration of melanoma cells. Western blot assay was performed to measure the protein expression of ITGA9, hexokinase 2 (HK2), and epithelial-mesenchymal transition (EMT)-related proteins in melanoma tissues or cells. The relationship among CCAT1, miR-296-3p, and ITGA9 was predicted and confirmed by bioinformatics analysis, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assay, respectively. A xenograft experiment was established to assess the effect of CCAT1 knockdown in vivo. RESULTS CCAT1 was effectively increased in melanoma tissues and cells compared with matched controls, and deficiency of CCAT1 impeded cell glycolysis, proliferation, migration while induced apoptosis, which were abrogated by knockdown of miR-296-3p in melanoma cells. In addition, our findings revealed that ITGA9 overexpression abolished miR-296-3p overexpression-induced effects on melanoma cells. Importantly, CCAT1 regulated ITGA9 expression by sponging miR-296-3p. The results of xenograft experiment suggested that CCAT1 silencing inhibited melanoma cell growth in vivo. CONCLUSION LncRNA CCAT1 promoted ITGA9 expression by sponging miR-296-3p in melanoma.
Collapse
Affiliation(s)
- Jinghua Fan
- Department of Dermatology, Xi’an Central Hospital Affiliated to Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Xiaoxiao Kang
- Department of Dermatology, Xi’an Central Hospital Affiliated to Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Limin Zhao
- Department of Dermatology, Xi’an Central Hospital Affiliated to Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Yan Zheng
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Jun Yang
- Department of Dermatology, Xi’an Central Hospital Affiliated to Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Di Li
- Department of Dermatology, Xi’an Central Hospital Affiliated to Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| |
Collapse
|
|
42
|
LncRNA MIAT Promotes Inflammation and Oxidative Stress in Sepsis-Induced Cardiac Injury by Targeting miR-330-5p/TRAF6/NF-κB Axis. Biochem Genet 2020; 58:783-800. [DOI: 10.1007/s10528-020-09976-9] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 05/30/2020] [Indexed: 11/27/2022]
|
|
43
|
Long non-coding RNA CCAT1 promotes colorectal cancer progression by regulating miR-181a-5p expression. Aging (Albany NY) 2020; 12:8301-8320. [PMID: 32380476 PMCID: PMC7244037 DOI: 10.18632/aging.103139] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 03/31/2020] [Indexed: 01/30/2023]
Abstract
The vital roles of long noncoding RNAs (lncRNAs) have been implicated in growing number of studies in tumor development. LncRNA CCAT1 has been recognized as associated with tumor development, yet its relation with colorectal cancer (CRC) remains elusive. Our study aimed at elucidating the function and mechanisms of long non-coding RNA CCAT1 in CRC. From a lncRNA profile dataset of 38 pairs of matched tumor-control colon tissues from colorectal patients housed in The Cancer Genome Atlas (TCGA), we detected 10 upregulated and 10 down-regulated lncRNAs in CRC. Fifty cases of CRC patients were enrolled to analyze the correlation between the expression of CCAT1 and clinical pathology. The inverse correlation of expression and target relationship between CCAT1 and miR-181a-5p were verified using qRT-PCR and dual-luciferase reporter gene assay. Cell viability, colony formation ability, aggression and apoptosis were determined by MTT assay, colony formation assay, Transwell and wound healing assays and flow cytometry analysis. Furthermore, Xenograft model was used to show that knockdown of CCAT1 inhibits tumor growth in vivo. The expression of lncRNA CCAT1 was significantly upregulated in CRC tissues. The CCAT1 expression was positively associated with cancer stage (American Joint Committee on Cancer stage, P<0.05). CCAT1 promoted cell proliferation, growth and mobility by targeting miR-181a-5p and the silence of CCAT1 increased the cell apoptosis. Same effect was observed in an in vivo xenograft model, which the tumor size and pro-tumor proteins were significantly diminished by knocking down of CCAT1.
Collapse
|
|
44
|
Li P, Yan X, Xu G, Pang Z, Weng J, Yin J, Li M, Yu L, Chen Q, Sun K. A novel plasma lncRNA ENST00000416361 is upregulated in coronary artery disease and is related to inflammation and lipid metabolism. Mol Med Rep 2020; 21:2375-2384. [PMID: 32323776 PMCID: PMC7185291 DOI: 10.3892/mmr.2020.11067] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 03/10/2020] [Indexed: 12/22/2022] Open
Abstract
Coronary artery disease (CAD) is a serious threat to human health and a major cause of mortality worldwide. Long noncoding RNAs (lncRNAs) affect the occurrence and development of CAD via the regulation of cell proliferation and apoptosis, inflammatory responses and lipid metabolism. Screening methods and therapeutic strategies for CAD have been extensively studied. The present study analyzed clinical indexes of 187 patients with CAD and 150 healthy subjects. The data showed significant differences in diabetes mellitus, hypertension, high-density lipoprotein level and smoking history between the CAD group and the control group. A series of differentially expressed lncRNAs were detected in the plasma samples of three patients with CAD by high-throughput sequencing. Reverse transcription-quantitative (RT-q)PCR data revealed that the expression level of the novel lncRNA ENST00000416361 was ~2.3-fold higher in the plasma of 50 patients with CAD compared with the 50 control subjects. Receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve was 0.7902. Knockdown of ENST00000416361 in human umbilical vein endothelial cells markedly downregulated interleukin-6 and tumor necrosis factor-α levels. In addition, sterol regulatory element binding transcription factor (SREBP)1 and SREBP2 were upregulated in patients with CAD, and they were positively correlated with the expression of ENST00000416361. RT-qPCR further demonstrated that knockdown of ENST00000416361 led to the downregulation of SREBP1 and SREBP2. Overall, the novel lncRNA ENST00000416361 may be associated with CAD-induced inflammation and lipid metabolism, and it may serve as a potential biomarker for CAD.
Collapse
Affiliation(s)
- Ping Li
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Xinxin Yan
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Guidong Xu
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Zhi Pang
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Jiayi Weng
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Juan Yin
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Meifen Li
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Lan Yu
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Qian Chen
- Institute of Digestive Diseases and Nutrition, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| | - Kangyun Sun
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, P.R. China
| |
Collapse
|
|
45
|
Yan Z, Yang Q, Xue M, Wang S, Hong W, Gao X. YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4. Cancer Cell Int 2020; 20:108. [PMID: 32280300 PMCID: PMC7126398 DOI: 10.1186/s12935-020-1157-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 02/29/2020] [Indexed: 12/26/2022] Open
Abstract
Background Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended. Methods The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony formation, EdU, CCK-8, transwell and wound healing as well as in vivo assays revealed the function of ZFPM2-AS1 in SCLC. ChIP, luciferase reporter, RIP and RNA pull down assays demonstrated the binding relation among genes. Results ZFPM2-AS1 was significantly upregulated in SCLC tissues and cells. ZFPM2-AS1 deficiency attenuated SCLC cell proliferation, invasion and migration. In addition, ZFPM2-AS1 was transcriptionally activated by Yin Yang 1 (YY1) factor. Further, miR-3612 was confirmed as downstream miRNA of ZFPM2-AS1. Moreover, TNF receptor associated factor 4 (TRAF4) was the target gene of miR-3612 in SCLC. ZFPM2-AS1, miR-3612 and TRAF4 jointly constituted a competing endogenous RNA (ceRNA) network in SCLC. Finally, TRAF4 could countervail ZFPM2-AS1 downregulation-mediated function on SCLC cell proliferation and invasion in vitro and tumor growth in vivo. Conclusion Our study elucidated the oncogenic effect of ZFPM2-AS1 in SCLC progression, indicating it may be a therapeutic target for SCLC.
Collapse
Affiliation(s)
- Zhijun Yan
- 1Department of Respiratory Medicine, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199 China
| | - Qilian Yang
- 2Department of Pharmacy, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199 China
| | - Min Xue
- 1Department of Respiratory Medicine, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199 China
| | - Sheng Wang
- 3Institutes of Biomedical Sciences, Fudan University, 131 Dongan Road, Shanghai, 200032 China
| | - Weijun Hong
- 1Department of Respiratory Medicine, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199 China
| | - Xiwen Gao
- 1Department of Respiratory Medicine, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199 China
| |
Collapse
|
|
46
|
Association of long non-coding RNA and leukemia: A systematic review. Gene 2020; 735:144405. [DOI: 10.1016/j.gene.2020.144405] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 01/27/2020] [Indexed: 12/12/2022]
|
|
47
|
Fattahi S, Kosari-Monfared M, Golpour M, Emami Z, Ghasemiyan M, Nouri M, Akhavan-Niaki H. LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine. J Cell Physiol 2020; 235:3189-3206. [PMID: 31595495 DOI: 10.1002/jcp.29260] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 09/03/2019] [Indexed: 02/06/2023]
Abstract
Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30-35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.
Collapse
Affiliation(s)
- Sadegh Fattahi
- Department of Genetics, Student Research Committee, Babol University of Medical Sciences, Babol, Iran
- Department of Genetics, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- Department of Biochemistry, North Research Center, Pasteur Institute, Amol, Iran
| | | | - Monireh Golpour
- Department of Immunology, Molecular and Cell Biology Research Center, Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zakieh Emami
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Ghasemiyan
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Nouri
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Haleh Akhavan-Niaki
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| |
Collapse
|
|
48
|
Li N, Hao W, Yang J, Guo Y, Guo Y, Du Y. Long non-coding RNA colon cancer-associated transcript-1 regulates tumor cell proliferation and invasion of non-small-cell lung cancer through suppressing miR-152. Geriatr Gerontol Int 2020; 20:629-636. [PMID: 32227563 DOI: 10.1111/ggi.13914] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 03/04/2020] [Accepted: 03/07/2020] [Indexed: 01/17/2023]
Abstract
AIM Lung cancer serves as one of the most common cancers in the world, and approximately 50% of non-small-cell lung cancer (NSCLC) patients are found to be aged >70 when diagnosed. In this study, we aimed to explore the effect of long non-coding RNAs colon cancer-associated transcript-1 (CCAT1) in NSCLC. METHODS A total of 72 clinical samples from older NSCLC patients were collected for analysis. The relative mRNA level of CCAT1 was detected through real-time polymerase chain reaction. Overall survival of NSCLC patients was detected through Kaplan-Meier survival analysis. MTT assays were used to detect cell proliferation. Cell invasion was determined by transwell assay. Protein levels were detected through western blot. RESULTS CCAT1 expression levels significantly increased in NSCLC tumor tissues and were associated with poor overall survival of NSCLC patients. CCAT1 promotes cell proliferation, cell invasion and epithelial-mesenchymal transition of NSCLC cell lines. CCAT1 binds with miR-152, and the effect of si-CCAT1 in NSCLC cell proliferation, cell invasion and epithelial-mesenchymal transition was partially reversed by anti-miR-152. CONCLUSIONS Long non-coding RNA CCAT1 regulates tumor cell proliferation and invasion in NSCLC through suppressing miR-152. Geriatr Gerontol Int 2020; ••: ••-••.
Collapse
Affiliation(s)
- Na Li
- Department of Clinical Medicine, College of Medicine, Pingdingshan University, Pingdingshan, China
| | - Weiwei Hao
- Department of Clinical Medicine, College of Medicine, Pingdingshan University, Pingdingshan, China
| | - Junfang Yang
- Department of Gastroenterology, First Affiliated Hospital of Pingdingshan University, Pingdingshan, China
| | - Yali Guo
- Department of Aspiration, First Affiliated Hospital of Pingdingshan University, Pingdingshan, China
| | - Yonggang Guo
- Department of Clinical Medicine, College of Medicine, Pingdingshan University, Pingdingshan, China
| | - Ying Du
- Department of Clinical Medicine, College of Medicine, Pingdingshan University, Pingdingshan, China
| |
Collapse
|
|
49
|
Zhao L, Wang L, Wang Y, Ma P. Long non‑coding RNA CCAT1 enhances human non‑small cell lung cancer growth through downregulation of microRNA‑218. Oncol Rep 2020; 43:1045-1052. [PMID: 32323859 PMCID: PMC7057767 DOI: 10.3892/or.2020.7500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Accepted: 11/23/2018] [Indexed: 01/19/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) have critical functions in non-small cell lung cancer (NSCLC) growth. In the present study, we showed that lncRNA-CCAT1 was upregulated in NSCLC tissues. High expression of lncRNA-CCAT1 was related to tumor growth and reduced survival rate. We used short hairpin RNAs (shRNAs) to inhibit the expression of lncRNA-CCAT1 in NSCLC cells. In vitro and in vivo results demonstrated that lncRNA-CCAT1 knockdown suppressed tumor proliferation and induced apoptosis. Furthermore, microRNA-218 (miR-218) was confirmed as an effective target of lncRNA-CCAT1 in NSCLC. B lymphoma Mo-MLV insertion region 1 homolog (BMI-1), which served as a downstream target of miR-218, was also inhibited by lncRNA-CCAT1 knockdown. In conclusion, the present study indicated that upregulation of lncRNA-CCAT1 in NSCLC is associated with tumor malignant potential. lncRNA-CCAT1 enhances tumor growth in NSCLC by directly inhibiting miR-218 and indirectly increasing BMI-1 expression.
Collapse
Affiliation(s)
- Lijiang Zhao
- Department of Respiratory Medicine, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
| | - Limin Wang
- Department of Respiratory Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P.R. China
| | - Yongfeng Wang
- Department of Respiratory Medicine, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
| | - Ping Ma
- Department of Respiratory Medicine, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
| |
Collapse
|
|
50
|
Gu C, Zou S, He C, Zhou J, Qu R, Wang Q, Qi J, Zhou M, Yan S, Ye Z. Long non-coding RNA CCAT1 promotes colorectal cancer cell migration, invasiveness and viability by upregulating VEGF via negative modulation of microRNA-218. Exp Ther Med 2020; 19:2543-2550. [PMID: 32256733 PMCID: PMC7086191 DOI: 10.3892/etm.2020.8518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 01/28/2020] [Indexed: 01/28/2023] Open
Abstract
Increasing evidence has demonstrated that long non-coding (lnc) RNA is aberrantly expressed in numerous types of cancer. Colorectal cancer is a common malignancy; however, the role and mechanism underlying the influence of lncRNA-colon cancer associated transcript 1 (CCAT1) in colorectal cancer is yet to be elucidated. The present study revealed that CCAT1 is highly expressed in colorectal cancer tissues. Bioinformatics analysis and a dual-luciferase reporter gene assay indicated that CCAT1 and microRNA (miR)-218 had complementary binding sites. Furthermore, reverse transcription-quantitative PCR revealed that miR-218 was downregulated in colorectal cancer tissues compared with paired adjacent healthy tissues. To investigate the biological effects of CCAT1 on colorectal cancer cells, MTT and Transwell assays were performed. The results revealed that when compared with the control group, CCAT1-short hairpin (sh)RNA significantly inhibited colorectal cancer cell (SW480) viability and decreased migration and invasiveness. In addition, CCAT1-shRNA significantly reduced vascular endothelial growth factor (VEGF) expression in SW480 cells; however, these effects were partially rescued by an miR-218 inhibitor. Furthermore, it was revealed that the CCAT1-plasmid significantly promoted the viability of SW480 cells, increased cell migration and invasiveness, and significantly increased VEGF expression. However, these effects were also partially rescued by with a miR-218 mimic. Taken together, the present results identified that the CCAT1/miR-218 axis serves a key role in the regulation of colorectal cancer progression, which may be used as potential therapeutic target for the treatment of colorectal cancer.
Collapse
Affiliation(s)
- Chao Gu
- Gastrointestinal Surgery Department, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Shitao Zou
- Suzhou Cancer Center Core Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Chao He
- Suzhou Cancer Center Core Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Jundong Zhou
- Suzhou Cancer Center Core Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Rui Qu
- Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Qin Wang
- Gastrointestinal Surgery Department, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Jie Qi
- Thyroid and Breast Surgery Department, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Ming Zhou
- General Surgery, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, Hubei 434020, P.R. China
| | - Shuai Yan
- Colorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu 215009, P.R. China
| | - Zhenyu Ye
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
| |
Collapse
|