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Ghorbani V, Ghorbian S. Gene expression profiling of lncRNA-HOTAIR and lncRNA-MALAT1 in esophageal cancer: uncovering links to lifestyle factors and diagnostic significance. Discov Oncol 2025; 16:630. [PMID: 40295320 PMCID: PMC12037955 DOI: 10.1007/s12672-025-02465-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 04/22/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Esophageal cancer (EC) is the sixth most common cause of cancer-related deaths globally. Genetic and environmental factors could be affected in EC's onset and development. The potential involvement of lncRNA-HOTAIR and lncRNA-MALAT1 in EC has garnered significant attention in recent studies. Our investigation aimed to examine lncRNA-HOTAIR and lncRNA-MALAT1 gene expression changes in EC patients. MATERIALS AND METHODS Our experimental study focused on 140 patients with malignant EC, comprising 70 paraffin-embedded tumor tissues (FFPE) blocks and 70 FFPE blocks with marginal tissue samples. The relative gene expression levels of lncRNA-HOTAIR and lncRNA-MALAT1 were measured using Real-Time PCR. The data were analyzed using ANOVA and 2-△△CT tests. RESULTS Our analysis revealed a significant increase in tumor expression compared to marginal tissues (P < 0.05). Besides, our research revealed a significant correlation between lncRNA-HOTAIR expression and hot drinks (P = 0.019), metastasis (P = 0.001), and the 5-year survival rate (P = 0.001). We found a significant correlation between lncRNA-MALAT1 expression and alcohol abuse (P = 0.039), hot drinks (P = 0.001), and metastasis (P = 0.039). CONCLUSION The findings indicate a potential carcinogenic effect of lncRNA-HOTAIR and lncRNA-MALAT1 gene expression alterations in EC patients. Also, studying the lncRNA genes can help us identify biomarkers, emphasizing the significance of early diagnosis and treatment.
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Affiliation(s)
- Vahid Ghorbani
- Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran
| | - Saeid Ghorbian
- Department of Biology, Ta.C., Islamic Azad University, Tabriz, Iran.
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2
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Sheng S, Guo J, Lu C, Hu X. Non-coding RNAs in thoracic disease: Barrett's esophagus and esophageal adenocarcinoma. Clin Chim Acta 2025; 571:120242. [PMID: 40074193 DOI: 10.1016/j.cca.2025.120242] [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: 01/31/2025] [Revised: 03/08/2025] [Accepted: 03/09/2025] [Indexed: 03/14/2025]
Abstract
Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with increasing incidence and poor survival rates, primarily due to late-stage diagnosis. This cancer often develops from Barrett's Esophagus (BE), a precancerous condition linked to chronic gastroesophageal reflux disease (GERD). The transition from BE to EAC is a complex multistep process involving numerous genetic, epigenetic, and molecular changes that lead to the malignant transformation of the esophageal epithelium. Despite advancements in understanding the molecular mechanisms underlying EAC, early detection and effective treatment options remain limited, highlighting an urgent need for innovative diagnostic and therapeutic strategies. Recent research has focused on non-coding RNAs (ncRNAs), which play crucial roles in regulating gene expression and cellular processes relevant to cancer progression. Various types of ncRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in the development of BE and EAC by modulating key signaling pathways such as Wnt/β-catenin and NF-κB. Additionally, ncRNAs are stable in biological fluids, presenting opportunities for their use as non-invasive biomarkers for early detection and monitoring of EAC. This review aims to elucidate the involvement of ncRNAs in the progression from BE to EAC, their potential as therapeutic targets, and their emerging roles in intercellular communication. We will also discuss the challenges in translating ncRNA research into clinical applications, emphasizing their promise in revolutionizing early detection and treatment strategies for EAC.
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Affiliation(s)
- Siyuan Sheng
- Department of Medicine, Hunan University of Arts and Science, Changde, Hunan Province 415000, China.
| | - Jianhui Guo
- Spine Surgery of Changde Second People's Hospital, Changde, Hunan Province 415000, China
| | - Chuangang Lu
- Sanya Central Hospital, Sanya, Hainan Province 572000, China
| | - Xia Hu
- Department of Medicine, Hunan University of Arts and Science, Changde, Hunan Province 415000, China
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3
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Sagaram M, Kallwitz ER. Linking Long ncRNA to the Diagnosis, Pathogenesis, and Prognosis of Esophageal Cancer. Dig Dis Sci 2025; 70:459-461. [PMID: 39826059 DOI: 10.1007/s10620-024-08817-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 12/19/2024] [Indexed: 01/20/2025]
Abstract
Esophageal cancer is a common and often deadly malignancy, with treatment success depending largely on the stage at the time of diagnosis. Recently, studies have examined the role of non-coding RNAs in esophageal cancer pathogenesis, prognosis and therapy. This perspective specifically examines interactions long non-coding RNAs have with other RNA molecules in various facets of esophageal cancer.
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Affiliation(s)
- Manasa Sagaram
- Department of Gastroenterology and Hepatology, Loyola University Medical Center, 2160 S First Ave, Maywood, IL, 60153, USA
| | - Eric R Kallwitz
- Department of Gastroenterology and Hepatology, Loyola University Medical Center, 2160 S First Ave, Maywood, IL, 60153, USA.
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4
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Naveed M, Malik A, Anjum H, Ijaz B. LncRNA MALAT1 Expression Regulates Breast Cancer Progression via PI3K/AKT/mTOR Pathway Modulation. Biochem Genet 2024; 62:3421-3438. [PMID: 38110774 DOI: 10.1007/s10528-023-10592-6] [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: 07/15/2023] [Accepted: 11/07/2023] [Indexed: 12/20/2023]
Abstract
Breast cancer is a significant health challenge for women globally, including the Pakistani population. Numerous pathways and small molecules like noncoding ribonucleotides are implicated in breast cancer development and progression. Among these, lncRNAs, have garnered considerable attention due to their role in breast cancer tumorigenesis and metastasis. In the current study involving 52 mammary tumor samples from the Pakistani population, the expression of lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) was studied via RT-PCR (Real-Time polymerase chain reaction). In addition, PI3K/AKT/mTOR pathway expression was also assessed through RT-PCR and immunohistochemistry in breast cancer patient samples. The study also investigated the cross-talk of lncRNA MALAT1 and PI3K pathway genes by inhibiting it with PI3K inhibitor (LY294002) in MDA-MB-231 cell line. Furthermore, lncRNA MALAT1 was silenced in MDA-MB-231 cells using siRNA to determine its impact on breast cancer proliferation and metastasis. The results revealed an upregulated expression of MALAT1 and PI3K/AKT/mTOR pathway genes in grade II and III breast tissue samples before chemotherapy. The proliferation, growth, and invasion of breast cancer cells were significantly reduced upon MALAT1 silencing in MDA-MB-231. Further, its downregulation substantially reduced the PI3K pathway expression levels at mRNA and protein levels. In conclusion, the current study suggests that MALAT1 could serve as a therapeutic target for breast cancer, underscoring its role in breast cancer proliferation and metastasis. Moreover, the study proposes a mechanism of action of MALAT1, demonstrating that its inhibition can reduce the expression of the PI3K/AKT/mTOR axis. These findings emphasize the potential significance of targeting MALAT1 as a therapeutic strategy for breast cancer, and further exploration of this interaction is warranted to gain deeper insight into the molecular mechanism of this lncRNA.
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Affiliation(s)
- Mariam Naveed
- Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Road Thokar Niaz Baig , Lahore, 53700, Pakistan
| | - Ayesha Malik
- Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Road Thokar Niaz Baig , Lahore, 53700, Pakistan
| | - Hamza Anjum
- Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Road Thokar Niaz Baig , Lahore, 53700, Pakistan
| | - Bushra Ijaz
- Laboratory of Applied and Functional Genomics, Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road, Lahore, 53700, Pakistan.
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5
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Zhang YT, Zhao LJ, Zhou T, Zhao JY, Geng YP, Zhang QR, Sun PC, Chen WC. The lncRNA CADM2-AS1 promotes gastric cancer metastasis by binding with miR-5047 and activating NOTCH4 translation. Front Pharmacol 2024; 15:1439497. [PMID: 39309008 PMCID: PMC11412803 DOI: 10.3389/fphar.2024.1439497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 08/26/2024] [Indexed: 09/25/2024] Open
Abstract
Background Multi-organ metastasis has been the main cause of death in patients with Gastric cancer (GC). The prognosis for patients with metastasized GC is still very poor. Long noncoding RNAs (lncRNAs) always been reported to be closely related to cancer metastasis. Methods In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected by Transwell, Wound healing, Western Blot or other assays in vitro and in vivo. Further mechanism study was performed by RNA FISH, Dual-luciferase reporter assay and RT-qPCR. Finally, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 in patient tissues was detected by RT-qPCR. Results In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected in vitro and in vivo. The results shown that overexpression of the lncRNA CADM2-AS1 promoted GC metastasis, while knockdown inhibited it. Further mechanism study proved that lncRNA CADM2-AS1 could sponge and silence miR-5047, which targeting mRNA was NOTCH4. Elevated expression of lncRNA CADM2-AS1 facilitate GC metastasis by up-regulating NOTCH4 mRNA level consequently. What's more, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 was further detected and verified in metastatic GC patient tissues. Conclusions LncRNA CADM2-AS1 promoted metastasis in GC by targeting the miR-5047/NOTCH4 signaling axis, which may be a potential target for GC metastasis.
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Affiliation(s)
- Yu-Tong Zhang
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou University People’s Hospital, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Li-Juan Zhao
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou University People’s Hospital, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
| | - Teng Zhou
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou University People’s Hospital, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jin-Yuan Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yin-Ping Geng
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Qiu-Rong Zhang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Pei-Chun Sun
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou University People’s Hospital, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
| | - Wen-Chao Chen
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou University People’s Hospital, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
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6
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Wu T, Dong Y, Yang X, Mo L, You Y. Crosstalk between lncRNAs and Wnt/β-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response. Noncoding RNA Res 2024; 9:667-677. [PMID: 38577016 PMCID: PMC10987302 DOI: 10.1016/j.ncrna.2024.02.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/24/2024] [Accepted: 02/21/2024] [Indexed: 04/06/2024] Open
Abstract
Lung cancer (LC) is considered to have the highest mortality rate around the world. Because there are no early diagnostic signs or efficient clinical alternatives, distal metastasis and increasing numbers of recurrences are a challenge in the clinical management of LC. Long non-coding RNAs (lncRNAs) have recently been recognized as a critical regulator involved in the progression and treatment response to LC. The Wnt/β-catenin pathway has been shown to influence LC occurrence and progress. Therefore, discovering connections between Wnt signaling pathway and lncRNAs may offer new therapeutic targets for improving LC treatment and management. In this review, the purpose of this article is to present possible therapeutic approaches by reviewing particular relationships, key processes, and molecules associated to the beginning and development of LC.
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Affiliation(s)
- Ting Wu
- Research Laboratory of Translational Medicine/Laboratory of Protein Structure and Function, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - YiRan Dong
- Research Laboratory of Translational Medicine/Laboratory of Protein Structure and Function, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - XinZhi Yang
- Research Laboratory of Translational Medicine/Laboratory of Protein Structure and Function, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Liang Mo
- Department of Thoracic Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Yong You
- Research Laboratory of Translational Medicine/Laboratory of Protein Structure and Function, Hengyang Medical School, University of South China, Hengyang, 421001, China
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7
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Hussain MS, Agrawal M, Shaikh NK, Saraswat N, Bahl G, Maqbool Bhat M, Khurana N, Bisht AS, Tufail M, Kumar R. Beyond the Genome: Deciphering the Role of MALAT1 in Breast Cancer Progression. Curr Genomics 2024; 25:343-357. [PMID: 39323624 PMCID: PMC11420562 DOI: 10.2174/0113892029305656240503045154] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 03/25/2024] [Accepted: 04/04/2024] [Indexed: 09/27/2024] Open
Abstract
The MALAT1, a huge non-coding RNA, recently came to light as a multifaceted regulator in the intricate landscape of breast cancer (BC) progression. This review explores the multifaceted functions and molecular interactions of MALAT1, shedding light on its profound implications for understanding BC pathogenesis and advancing therapeutic strategies. The article commences by acknowledging the global impact of BC and the pressing need for insights into its molecular underpinnings. It is stated that the core lncRNA MALAT1 has a range of roles in both healthy and diseased cell functions. The core of this review unravels MALAT1's multifaceted role in BC progression, elucidating its participation in critical processes like resistance, invasion, relocation, and proliferating cells to therapy. It explores the intricate mechanisms through which MALAT1 modulates gene expression, interacts with other molecules, and influences signalling pathways. Furthermore, the paper emphasizes MALAT1's clinical significance as a possible prognostic and diagnostic biomarker. Concluding on a forward-looking note, the review highlights the broader implications of MALAT1 in BC biology, such as its connections to therapy resistance and metastasis. It underscores the significance of deeper investigations into these intricate molecular interactions to pave the way for precision medicine approaches. This review highlights the pivotal role of MALAT1 in BC progression by deciphering its multifaceted functions beyond the genome, offering profound insights into its implications for disease understanding and the potential for targeted therapeutic interventions.
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Affiliation(s)
- Md Sadique Hussain
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan (302017), India
| | - Mohit Agrawal
- Department of Pharmacology, School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram 122103, India
| | - Nusratbanu K. Shaikh
- Department of Quality Assurance, Smt. N. M. Padalia Pharmacy College, Ahmedabad, 382210, Gujarat, India
| | - Nikita Saraswat
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan (302017), India
| | - Gurusha Bahl
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan (302017), India
| | - Mudasir Maqbool Bhat
- Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, India
| | - Navneet Khurana
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Ajay Singh Bisht
- School of Pharmaceutical Sciences, Shri Guru Ram Rai University, Patel Nagar, Dehradun, Uttarakhand (248001), India
| | - Muhammad Tufail
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Rajesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
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8
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Manawy SM, Faruk EM, Hindawy RF, Hassan MM, Farrag DMG, Bashar MAE, Fouad H, Bagabir RA, Hassan DAA, Zaazaa AM, Hablas MGA, Kamal KM. Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone). Tissue Cell 2024; 87:102330. [PMID: 38412579 DOI: 10.1016/j.tice.2024.102330] [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: 01/08/2024] [Revised: 02/08/2024] [Accepted: 02/13/2024] [Indexed: 02/29/2024]
Abstract
The current study was conducted to determine the precise mechanisms of Sirtuin-1 (Sirt-1), TGF- β (Transforming Growth Factor-β), and long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (LncRNA MALAT-1) in signaling pathways in doxorubicin (DOX)-induced nephrotoxicity. The potential therapeutic effect of Resveratrol and Pirfenidone in DOX toxicity was also assessed. Thirty-six male adult rats were evenly distributed into four groups: Group 1: control rats. Group 2: DOX exposed rats' group, each animal received 7.5 mg/kg DOX as a single intravenous dose, Group 3: DOX exposed group subjected to oral resveratrol (20 mg/kg/daily for two weeks), Group 4: DOX exposed group subjected to oral Pirfenidone (200 mg/kg once daily for 10 days). At the planned time, animals were sacrificed. Renal tissue was collected to assess matrix metalloproteinase-9 (MMP9), inflammatory and apoptotic markers: tumor necrosis factor-alpha (TNF- β, caspase-3, cyclo-oxygenase-2 (COX-2), and oxidative stress markers: nitric oxide (NO), Glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). Sirtuin-1 (Sirt-1), TGF-β, and LncRNA MALAT-1 were quantitatively assessed by real-time RT-PCR in the whole blood. Results showed that the DOX group exhibited a significant increase in oxidative stress markers, and inflammatory, and apoptotic markers in the renal tissue. Histologically, the renal tubule lining cells exhibited vacuolar alterations in the cytoplasm, glomerular atrophy, and vascular congestion. Furthermore, renal degeneration was evident, as confirmed by the heightened immuno-expression of MMP9. Exposure to DOX resulted in a significant decrease in Sirtuin-1 (Sirt-1) with a significant increase in the TGFβ, and LncRNA MALAT-1 gene expression. However, pre-treatment with either resveratrol/or Pirefenidone ameliorated the histological renal alterations, regulated the pathways of Sirt-1, TGFβ, and LncRNA MALAT-1, and decreased all oxidative stress, inflammatory and apoptotic markers. In conclusion, DOX exposure leads to renal toxicity by inducing renal degeneration, oxidative stress, and apoptosis. Administration of either resveratrol or Pirfenidone counteracted these changes and protected the kidney against DOX-induced renal damage.
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Affiliation(s)
- Samia Mahmoud Manawy
- Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha, Egypt.
| | - Eman Mohamed Faruk
- Anatomy Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt.
| | - Rabab Fawzy Hindawy
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha, Egypt.
| | - Mahmoud M Hassan
- Department of Physiology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Diaa M G Farrag
- Marine Biology Branch, Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt.
| | - Mansour A E Bashar
- Marine Biology Branch, Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt.
| | - Hanan Fouad
- Basic Medical Sciences, Faculty of Medicine, Galala University, Galala City, POB 43711, ATTAKA, Suez Governorate, Egypt; Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo POB 12613, Egypt.
| | - Rania Abubaker Bagabir
- College of Medicine, Hematology and Immunology Department, Umm Al-Qura University, Makkah, Saudi Arabia
| | | | - Ahmed Mohammed Zaazaa
- Students at Faculty of Medicine, Benha National University, Benha Colleges in Cairo, Egypt
| | | | - K Mostafa Kamal
- Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha, Egypt
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9
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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.
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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.
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10
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Imran M, Abida, Eltaib L, Siddique MI, Kamal M, Asdaq SMB, Singla N, Al-Hajeili M, Alhakami FA, AlQarni AF, Abdulkhaliq AA, Rabaan AA. Beyond the genome: MALAT1's role in advancing urologic cancer care. Pathol Res Pract 2024; 256:155226. [PMID: 38452585 DOI: 10.1016/j.prp.2024.155226] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Urologic cancers (UCs), which include bladder, kidney, and prostate tumors, account for almost a quarter of all malignancies. Long non-coding RNAs (lncRNAs) are tissue-specific RNAs that influence cell growth, death, and division. LncRNAs are dysregulated in UCs, and their abnormal expression may allow them to be used in cancer detection, outlook, and therapy. With the identification of several novel lncRNAs and significant exploration of their functions in various illnesses, particularly cancer, the study of lncRNAs has evolved into a new obsession. MALAT1 is a flexible tumor regulator implicated in an array of biological activities and disorders, resulting in an important research issue. MALAT1 appears as a hotspot, having been linked to the dysregulation of cell communication, and is intimately linked to cancer genesis, advancement, and response to treatment. MALAT1 additionally operates as a competitive endogenous RNA, binding to microRNAs and resuming downstream mRNA transcription and operation. This regulatory system influences cell growth, apoptosis, motility, penetration, and cell cycle pausing. MALAT1's evaluation and prognosis significance are highlighted, with a thorough review of its manifestation levels in several UC situations and its association with clinicopathological markers. The investigation highlights MALAT1's adaptability as a possible treatment target, providing fresh ways for therapy in UCs as we integrate existing information The article not only gathers current knowledge on MALAT1's activities but also lays the groundwork for revolutionary advances in the treatment of UCs.
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Affiliation(s)
- Mohd Imran
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
| | - Abida
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Lina Eltaib
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Muhammad Irfan Siddique
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Mehnaz Kamal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | | | - Neelam Singla
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur 302017, India
| | - Marwan Al-Hajeili
- Department of Medicine, King Abdulaziz University, Jeddah 23624, Saudi Arabia
| | - Fatemah Abdulaziz Alhakami
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Saudi Arabia
| | - Ahmed Farhan AlQarni
- Histopathology Laboratory, Najran Armed Forces Hospital, Najran 66251, Saudi Arabia
| | - Altaf A Abdulkhaliq
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
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11
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Syllaios A, Gazouli M, Vailas M, Mylonas KS, Sakellariou S, Sougioultzis S, Karavokyros I, Liakakos T, Schizas D. The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma. Int J Mol Sci 2023; 25:98. [PMID: 38203269 PMCID: PMC10778904 DOI: 10.3390/ijms25010098] [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: 10/18/2023] [Revised: 12/09/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.
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Affiliation(s)
- Athanasios Syllaios
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | - Maria Gazouli
- Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Michail Vailas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | | | - Stratigoula Sakellariou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Stavros Sougioultzis
- Gastroenterology Unit, Department of Pathophysiology, School of Medicine, National and Kapodistrian University Athens, 115 27 Athens, Greece;
| | - Ioannis Karavokyros
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | - Theodoros Liakakos
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
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12
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Batista DMDO, da Silva JMC, Gigek CDO, Smith MDAC, de Assumpção PP, Calcagno DQ. Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression. World J Gastrointest Oncol 2023; 15:1520-1530. [PMID: 37746646 PMCID: PMC10514724 DOI: 10.4251/wjgo.v15.i9.1520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/30/2023] [Accepted: 07/27/2023] [Indexed: 09/13/2023] Open
Abstract
Gastric cancer (GC) remains among the most common cancers worldwide with a high mortality-to-incidence ratio. Accumulated evidence suggests that long noncoding RNAs (lncRNAs) are involved in gastric carcinogenesis. These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels, inducing or inhibiting biological processes and diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression. This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins. In the present review, we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC. Moreover, we highlighted the potential use of MALAT1 as a biomarker, including liquid biopsy.
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Affiliation(s)
| | | | | | - Marília de Arruda Cardoso Smith
- Disciplina de Genética,Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo 04023-900, São Paulo, Brazil
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13
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Hosseini SA, Haddadi MH, Fathizadeh H, Nemati F, Aznaveh HM, Taraj F, Aghabozorgizadeh A, Gandomkar G, Bazazzadeh E. Long non-coding RNAs and gastric cancer: An update of potential biomarkers and therapeutic applications. Biomed Pharmacother 2023; 163:114407. [PMID: 37100014 DOI: 10.1016/j.biopha.2023.114407] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/12/2023] [Accepted: 02/15/2023] [Indexed: 04/28/2023] Open
Abstract
The frequent metastasis of gastric cancer (GC) complicates the cure and therefore the development of effective diagnostic and therapeutic approaches is urgently necessary. In recent years, lncRNA has emerged as a drug target in the treatment of GC, particularly in the areas of cancer immunity, cancer metabolism, and cancer metastasis. This has led to the demonstration of the importance of these RNAs as prognostic, diagnostic and therapeutic agents. In this review, we provide an overview of the biological activities of lncRNAs in GC development and update the latest pathological activities, prognostic and diagnostic strategies, and therapeutic options for GC-related lncRNAs.
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Affiliation(s)
- Sayedeh Azimeh Hosseini
- Department of Medical Biotechnology, School of Advanced Technology, Shahrekord University of Medical Sciences, Shahrekord, Iran; Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran; USERN office, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | | | - Hadis Fathizadeh
- Student Research Committee, Sirjan School of Medical Sciences, Sirjan, Iran; Department of Laboratory sciences, Sirjan School of Medical Sciences, Sirjan, Iran
| | - Foroogh Nemati
- Department of Microbiology, Kashan University of Medical Sciences, Kashan, Iran
| | - Hooman Mahmoudi Aznaveh
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran
| | - Farima Taraj
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - AmirArsalan Aghabozorgizadeh
- Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | - Golmaryam Gandomkar
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Elaheh Bazazzadeh
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran
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14
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Geng H, Qian R, Zhang L, Yang C, Xia X, Wang C, Zhao G, Zhang Z, Zhu C. Clinical outcomes and potential therapies prediction of subgroups based on a ferroptosis-related long non-coding RNA signature for gastric cancer. Aging (Albany NY) 2022; 14:6358-6376. [PMID: 35969182 PMCID: PMC9417219 DOI: 10.18632/aging.204227] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 07/26/2022] [Indexed: 01/17/2023]
Abstract
Background: Gastric cancer (GC) is one of the most aggressive malignant tumors worldwide. Ferroptosis is a kind of iron-dependent cell death, which is proved to be closely related to tumor progression. In this study, we aim at constructing a ferroptosis-related lncRNAs signature to predict the prognosis of GC and explore potential therapies. Methods: Ferroptosis-Related LncRNAs Signature for GC patients (FRLSG) was constructed through univariate Cox regression, the LASSO algorithm, and multivariate Cox regression. Kaplan–Meier analysis, receiver operating characteristic curves, and risk score plot were applied to verify the predictive power of FRLSG. Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses were conducted to explore the potential clinical value of the FRLSG. In addition, drug sensitivity prediction was applied to identify chemotherapeutic drugs with potential therapeutic effect. Results: Five ferroptosis-related lncRNAs (AC004816.1, AC005532.1, LINC01357, AL355574.1 and AL049840.4) were identified to construct FRLSG, whose expression level in GC were confirmed by experimental validation. Kaplan-Meier curve and ROC curve proved the reliability and effectiveness of the FRLSG in predicting the prognosis for GC patients. Several immune-related pathways were enriched in the high-FRLSG group, and further immune infiltration analyses demonstrated the high immune infiltration status of the high-FRLSG group. In addition, 19 and 24 candidate drugs with potential therapeutic effect were identified for the high- and low-FRLSG groups, respectively. Conclusions: FRLSG was an effective tool in predicting the prognosis of GC, which might help to prioritize potential therapeutics for GC patients.
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Affiliation(s)
- Haigang Geng
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ruolan Qian
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Linmeng Zhang
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Yang
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiang Xia
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Cun Wang
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gang Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zizhen Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chunchao Zhu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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15
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Roshani M, Jafari A, Loghman A, Sheida AH, Taghavi T, Tamehri Zadeh SS, Hamblin MR, Homayounfal M, Mirzaei H. Applications of resveratrol in the treatment of gastrointestinal cancer. Biomed Pharmacother 2022; 153:113274. [PMID: 35724505 DOI: 10.1016/j.biopha.2022.113274] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/28/2022] [Accepted: 06/08/2022] [Indexed: 12/15/2022] Open
Abstract
Natural product compounds have lately attracted interest in the scientific community as a possible treatment for gastrointestinal (GI) cancer, due to their anti-inflammatory and anticancer properties. There are many preclinical, clinical, and epidemiological studies, suggesting that the consumption of polyphenol compounds, which are abundant in vegetables, grains, fruits, and pulses, may help to prevent various illnesses and disorders from developing, including several GI cancers. The development of GI malignancies follows a well-known path, in which normal gastrointestinal cells acquire abnormalities in their genetic composition, causing the cells to continuously proliferate, and metastasize to other sites, especially the brain and liver. Natural compounds with the ability to affect oncogenic pathways might be possible treatments for GI malignancies, and could easily be tested in clinical trials. Resveratrol is a non-flavonoid polyphenol and a natural stilbene, acting as a phytoestrogen with anti-cancer, cardioprotective, anti-oxidant, and anti-inflammatory properties. Resveratrol has been shown to overcome resistance mechanisms in cancer cells, and when combined with conventional anticancer drugs, could sensitize cancer cells to chemotherapy. Several new resveratrol analogs and nanostructured delivery vehicles with improved anti-GI cancer efficacy, absorption, and pharmacokinetic profiles have already been developed. This present review focuses on the in vitro and in vivo effects of resveratrol on GI cancers, as well as the underlying molecular mechanisms of action.
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Affiliation(s)
- Mohammad Roshani
- Internal Medicine and Gastroenterology, Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ameneh Jafari
- Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran; Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Amir Hossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | | | | | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
| | - Mina Homayounfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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16
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Yang Z, Xia L. Resveratrol inhibits the proliferation, invasion, and migration, and induces the apoptosis of human gastric cancer cells through the MALAT1/miR-383-5p/DDIT4 signaling pathway. J Gastrointest Oncol 2022; 13:985-996. [PMID: 35837196 DOI: 10.21037/jgo-22-307] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/27/2022] [Indexed: 11/06/2022] Open
Abstract
Background We aimed to study the effects and potential mechanism of resveratrol (RS) in gastric cancer (GC). Methods The human GC cell line SGC7901 was treated with different concentrations of RS (0, 1, 5 µM) for 24 hours. The messenger ribonucleic acid or protein expressions levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), micro ribonucleic acid-383-5p (miR-383-5p), and DNA damage-inducible transcript 4 (DDIT4) in GC cells were determined by Western blot and quantitative real-time polymerase chain assays. Cells were then transfected with miR-383-5p inhibitor (inhibitor), inhibitor negative control (NC), MALAT1-interfering RNA (si-MALAT1), si-DDIT4 and negative interference control (si-NC). The Cell Counting Kit-8 method, scratch assay, and transwell assay were performed to evaluate cell proliferation, migration, and invasion. Additionally, flow cytometry was used to examine apoptosis, and the target relationship was examined by a luciferase-reporter gene analysis. Results RS treatment downregulated the expression of MALAT1, repressed cell proliferation, inhibited cell migration and invasion (all P<0.05), and induced apoptosis (P<0.05) in GC cells. When the cells were treated with RS and inhibited the expression of MALAT1 meanwhile, the above anti-cancer effects were more significant (all P<0.05). Target prediction and the luciferase-reporter gene analysis showed that MALAT1 targeted miR-383-5p (P<0.05). When suppressing the expression of MALAT1 and miR-383-5p, the anti-cancer effects caused by the silencing of MALAT1 were absent (all P<0.05). We also found that miR-383-5p targeted DDIT4 protein. When the expression of miR-383-5p and DDIT4 in the GC cells was inhibited, the promoting cancer effects caused by the inhibition of miR-383-5p were reversed (all P<0.05). Conclusions This study found that RS inhibited the proliferation, migration, and invasion of human GC cells through the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-383-5p/DDIT4 pathway and induced apoptosis.
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Affiliation(s)
- Zhuying Yang
- Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Liang Xia
- Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China
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17
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Cheng Q, Zhang S, Zhong B, Chen Z, Peng F. Asiatic acid re-sensitizes multidrug-resistant A549/DDP cells to cisplatin by down regulating long non-coding RNA metastasis associated lung adenocarcinoma transcript 1/β-catenin signaling. Bioengineered 2022; 13:12972-12984. [PMID: 35609308 PMCID: PMC9275950 DOI: 10.1080/21655979.2022.2079302] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Drug resistance becomes a challenge in the therapeutic management of non-small cell lung cancer (NSCLC). According to our former research, asiatic acid (AA) re-sensitized A549/DDP cells to cisplatin (DDP) through decreasing multidrug resistance protein 1 (MDR1) expression level. However, the relevant underlying mechanisms are still unclear. Long non-coding RNA (lncRNA) MALAT1 shows close association with chemo-resistance. As reported in this research, AA increased apoptosis rate, down regulated the expression of MALAT1, p300, β-catenin, and MDR1, up regulated the expression of miR-1297, and decreased β-catenin nuclear translocation in A549/DDP cells. MALAT1 knockdown expression abolished the drug resistance of A549/DDP cells and increased cell apoptosis. MALAT1 could potentially produce interactions with miR-1297, which targeted to degradation of p300. In addition, p300 overexpression effectively rescued the effects of MALAT1 knockdown expression on A549/DDP cells and activate the expression of β-catenin/MDR1 signaling, and these could be effectively blocked by AA treatment. Conclusively, AA could re-sensitize A549/DDP cells to DDP through down-regulating MALAT1/miR-1297/p300/β-catenin signaling.
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Affiliation(s)
- Qilai Cheng
- College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Shanshan Zhang
- College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Bing Zhong
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Zhixi Chen
- College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Fang Peng
- Department of Pathology, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
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18
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Han Y, Zhao G, Shi X, Wang Y, Wen X, Zhang L, Guo X. The Emerging Role of Long Non-Coding RNAs in Esophageal Cancer: Functions in Tumorigenesis and Clinical Implications. Front Pharmacol 2022; 13:885075. [PMID: 35645836 PMCID: PMC9137892 DOI: 10.3389/fphar.2022.885075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 04/12/2022] [Indexed: 11/17/2022] Open
Abstract
Esophageal cancer (EC) is one of the most common malignancies of digestive tracts with poor five-year survival rate. Hence, it is very significant to further investigate the occurrence and development mechanism of esophageal cancer, find more effective biomarkers and promote early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) are generally defined as non-protein-coding RNAs with more than 200 nucleotides in length. Existing researches have shown that lncRNAs could act as sponges, guides, scaffolds, and signal molecules to influence the oncogene or tumor suppressor expressions at transcriptional, post-transcriptional, and protein levels in crucial cellular processes. Currently, the dysregulated lncRNAs are reported to involve in the pathogenesis and progression of EC. Importantly, targeting EC-related lncRNAs through genome editing, RNA interference and molecule drugs may be one of the most potential therapeutic methods for the future EC treatment. In this review, we summarized the biological functions and molecular mechanisms of lncRNAs, including oncogenic lncRNAs and tumor suppressor lncRNAs in EC. In addition, we generalized the excellent potential lncRNA candidates for diagnosis, prognosis and therapy in EC. Finally, we discussed the current challenges and opportunities of lncRNAs for EC.
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Affiliation(s)
- Yali Han
- Departments of Physiology, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Guo Zhao
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xinhang Shi
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Yushan Wang
- Departments of Physiology, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xin Wen
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Lu Zhang
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xiangqian Guo
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
- *Correspondence: Xiangqian Guo,
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19
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MALAT1-related signaling pathways in colorectal cancer. Cancer Cell Int 2022; 22:126. [PMID: 35305641 PMCID: PMC8933897 DOI: 10.1186/s12935-022-02540-y] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 03/05/2022] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most lethal and prevalent solid malignancies worldwide. There is a great need of accelerating the development and diagnosis of CRC. Long noncoding RNAs (lncRNA) as transcribed RNA molecules play an important role in every level of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a highly conserved nucleus-restricted lncRNA that regulates genes at the transcriptional and post-transcriptional levels. High expression of MALAT1 is closely related to numerous human cancers. It is generally believed that MALAT1 expression is associated with CRC cell proliferation, tumorigenicity, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis. Therefore, MALAT1 can be a potent gene for cancer prediction and diagnosis. In this review, we will demonstrate signaling pathways associated with MALAT1 in CRC.
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20
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Zhang W, Zhang L, Cai XJ, Li D, Cao FJ, Zuo ZG, Song Y, Yu XJ, Liu S. Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down-regulation of lncRNA MALAT1. Kaohsiung J Med Sci 2022; 38:585-593. [PMID: 35199933 DOI: 10.1002/kjm2.12506] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/19/2021] [Accepted: 01/12/2022] [Indexed: 12/19/2022] Open
Abstract
This study aims to evaluate the effect of dexmedetomidine (DEX)-on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), Annexin V-FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki-67 and active caspase-3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose-dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial-mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down-regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up-regulation of Ki-67 and the down-regulation of active caspase-3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.
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Affiliation(s)
- Wei Zhang
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Li Zhang
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiao-Jun Cai
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Dong Li
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Feng-Jun Cao
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Zhi-Gang Zuo
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Ying Song
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiong-Jie Yu
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Shan Liu
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
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Syllaios A, Sakellariou S, Garmpis N, Sarlani E, Damaskos C, Apostolou K, Kykalos S, Gazouli M, Karavokyros I, Schizas D. The role of miR-101 in esophageal and gastric cancer. Per Med 2021; 18:491-499. [PMID: 34402321 DOI: 10.2217/pme-2021-0024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 07/02/2021] [Indexed: 12/22/2022]
Abstract
miR-101 is downregulated in various types of cancer, leading to the notion that miR-101 acts as a suppressor in cancer cell progression. The comprehensive mechanisms underlying the effects of miR-101 and the exact role of miR-101 dysregulations in esophagogastric tumors have not been fully elucidated. This review aims to summarize all current knowledge on the association between miR-101 expression and esophagogastric malignancies and to clarify the pathogenetic pathways and the possible prognostic and therapeutic role of miR-101 in those cancer types. miR-101 seems to play crucial role in esophageal and gastric cancer biology and tumorigenesis. It could also be a promising novel diagnostic and therapeutic target, as well as it may serve as a significant predictive biomarker in esophagogastric cancer.
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Affiliation(s)
- Athanasios Syllaios
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Stratigoula Sakellariou
- First Department of Pathology, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Nikolaos Garmpis
- Second Propedeutic Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Eleni Sarlani
- First Department of Pathology, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Christos Damaskos
- N.S. Christeas Laboratory of Experimental Surgery & Surgical Research, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Konstantinos Apostolou
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Stylianos Kykalos
- Second Propedeutic Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National & Kapodistrian University of Athens, Athens, 11527, Greece
| | - Ioannis Karavokyros
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Dimitrios Schizas
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
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Chai Y, Liu S, Xie M. Interaction among long non-coding RNA, micro-RNA and mRNA in glioma. IBRAIN 2021; 7:141-145. [PMID: 37786911 PMCID: PMC10528991 DOI: 10.1002/j.2769-2795.2021.tb00076.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/25/2021] [Accepted: 06/24/2021] [Indexed: 10/04/2023]
Abstract
With the rapid development and wide application of gene sequencing, biotechnology, and informatics about cancer, it has been found that the main causes of malignant gliomas occurrence not only consist of abnormal mutations of protein-coding genes but also abnormal expressions of non-coding RNA (ncRNA). In this review, we summarize the interaction and mechanism between lncRNA-miRNA-mRNA and gliomas in occurrence, development, aggression, and migration in depth.
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Affiliation(s)
- Yang Chai
- Department of NeurosurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
| | - Shun Liu
- Department of NeurosurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
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