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Mahboobnia K, Kabir TD, Hou R, Liu P, Forrest A, Beveridge DJ, Richardson KL, Stuart LM, Yeoh GC, Leedman PJ. MicroRNA-142-3p Overcomes Drug Resistance in Hepatocellular Carcinoma by Targeting YES1 and TWF1. Int J Mol Sci 2025; 26:4161. [PMID: 40362400 PMCID: PMC12071648 DOI: 10.3390/ijms26094161] [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: 02/09/2025] [Revised: 04/16/2025] [Accepted: 04/16/2025] [Indexed: 05/15/2025] Open
Abstract
Resistance to tyrosine kinase inhibitors (TKIs, e.g., sorafenib and lenvatinib) presents a significant hurdle for hepatocellular carcinoma (HCC) treatment, underscoring the need to decipher the underlying mechanisms for improved therapeutic strategies. MicroRNAs (miRNAs) have emerged as critical modulators in HCC progression and TKI resistance. In this study, we report a positive correlation between the expression levels of a tumor suppressor miRNA, miR-142-3p, and increased sensitivity to sorafenib and lenvatinib, supported by clinical data from the BIOSTORM HCC cohort. Overexpression of miR-142-3p in TKI-resistant HCC cells significantly inhibited proliferation and colony formation, induced apoptosis, increased cell cycle arrest at the G2 phase, and reduced migration and invasion by reversing epithelial-mesenchymal transition. Notably, combining miR-142-3p with lenvatinib synergistically inhibited growth in both inherent and acquired TKI-resistant HCC cells by modulating critical signaling pathways, including STAT3, PI3K/AKT, MAPK, YAP1, and by impeding autophagic influx. RNA-sequencing of a TKI-resistant HCC cell line ± miR-142-3p overexpression identified YES1 and TWF1 as direct downstream target genes of miR-142-3p, both of which are key genes associated with drug resistance in HCC. Small interfering RNA (siRNA)-mediated knockdown of these genes mirrored the antitumor effects of miR-142-3p and enhanced TKI sensitivity, with YES1 knockdown decreasing YAP1 phosphorylation, and TWF1 knockdown inhibiting autophagy. Collectively, these findings indicate that restoring miR-142-3p expression or targeting its downstream effectors YES1 and TWF1 offers a promising strategy to overcome drug resistance and improve therapeutic outcome in HCC.
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Affiliation(s)
- Khadijeh Mahboobnia
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
| | - Tasnuva D. Kabir
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
| | - Rui Hou
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
| | - Peiwen Liu
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
| | - Alistair Forrest
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
| | - Dianne J. Beveridge
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
| | - Kirsty L. Richardson
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
| | - Lisa M. Stuart
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
| | - George C. Yeoh
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia
| | - Peter J. Leedman
- Harry Perkins Institute of Medical Research, QEII Medical Centre, 6 Verdun St, Nedlands, Perth, WA 6009, Australia; (K.M.); (T.D.K.); (R.H.); (P.L.); (A.F.); (D.J.B.); (K.L.R.); (L.M.S.); (G.C.Y.)
- Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
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Liao L, Yi Q, Zhao Z, Xu M, Wu T, Chen S, Liu Y. miR-6844/HSD17B13 Axis Contributes the Malignant Phenotype of Hepatocellular Carcinoma Cells. Cell Biol Int 2025. [PMID: 40255210 DOI: 10.1002/cbin.70025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 04/03/2025] [Accepted: 04/09/2025] [Indexed: 04/22/2025]
Abstract
Hepatocellular carcinoma (HCC) is a prevalent form of primary liver cancer, and aberrant miRNAs expression significantly contributes to its progression. Although the abnormal expression of miR-6844 in HCC has been reported, its impact on the malignant phenotype of HCC cells and its potential mechanism remains unclear. In this study, we initially conducted a bioinformatics analysis to investigate the differential expression of miR-6844 in HCC tissues and its impact on patient prognosis. The association between miR-6844 expression levels and clinical characteristics of HCC patients was subsequently investigated by integrating data from clinical samples. Ultimately, the impact of miR-6844 on the malignant phenotype of HCC cells and the underlying mechanisms were examined through in vitro cellular experiments. The results showed that a high expression of miR-6844 in HCC, which was associated with poor prognosis and exhibited significant correlations with intrahepatic metastasis and clinical stage among patients. The upregulation of miR-6844 promoted the proliferation, migration, and invasion of HCC cells while suppressing apoptosis. Conversely, the downregulation of miR-6844 significantly attenuated the malignant phenotype of HCC cells. In addition, HSD17B13 was identified as a target gene of miR-6844, and the overexpression of HSD17B13 partially counteracted the oncogenic effects induced by miR-6844 in HCC cells, otherwise the opposite. Taken together, the above results suggest that miR-6844 plays a regulatory role in the malignant phenotype of HCC cells through its targeting of HSD17B13.
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Affiliation(s)
- Li Liao
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
| | - Qilin Yi
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
| | - Zhen Zhao
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
| | - Ming Xu
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
| | - Tao Wu
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
| | - Shuai Chen
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
| | - Yu Liu
- Department of Hepatobiliary Surgery, Yueyang Central Hospital, Yueyang, Hunan, People's Republic of China
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He C, Hu Q, Liu C, Chu Y, Jia J, Zhang X, Niu Q. Aluminum Induces Neurotoxicity through the MicroRNA-98-5p/Insulin-like Growth Factor 2 Axis. ACS Chem Neurosci 2025; 16:329-341. [PMID: 39804702 DOI: 10.1021/acschemneuro.4c00429] [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] [Indexed: 02/06/2025] Open
Abstract
Aluminum is a well-known and widely distributed environmental neurotoxin. This study aimed to investigate the effect of miR-98-5p targeting insulin-like growth factor 2 (IGF2) on aluminum neurotoxicity. Thirty-two Sprague-Dawley rats were randomly divided into four groups and administered 0, 10, 20, and 40 μmol/kg maltol aluminum [Al(mal)3], respectively. They were intraperitoneally injected every other day for three months. PC12 cells were divided into four dose groups: 0, 100, 200, and 400 μmol/L Al(mal)3, and four intervention groups: inhibitor NC, Al(mal)3 + inhibitor NC, miR-98-5p inhibitor, and Al(mal)3 + miR-98-5p inhibitor. The Morris water maze was used to test the learning and memory abilities of rats. Hematoxylin and eosin staining was used to observe the arrangement and quantity of neurons in the CA1 area of the rat hippocampus. Cell viability was detected using the Cell Counting Kit-8. Cell apoptosis was detected using flow cytometry and the 5-ethynyl-2'-deoxyuridine assay. Real-time polymerase chain reaction and Western blotting were used to detect the expression levels of miR-98-5p, IGF2 mRNA, IGF2/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway proteins, and apoptosis-related proteins caspase3 and cleaved caspase3. The dual-luciferase assay was used to determine the targeting relationship between miR-98-5p and IGF2 mRNA. As the dose of aluminum exposure increased, the escape latency of rats gradually prolonged, and the target quadrant residence time and the number of crossing platforms gradually decreased. The arrangement of neurons in the hippocampal CA1 area was significantly loose, and their number gradually decreased. The total and early apoptosis rates of PC12 cells gradually increased, and the cell proliferation rate slowed down. Both in vivo and in vitro experimental results showed that with the increase of aluminum exposure dose, the relative expression levels of miR-98-5p and caspase3 and cleaved caspase3 proteins gradually increased, while the relative expression levels of IGF2 mRNA and IGF2, p-JAK2 (Tyr1007/1008), and p-STAT3 (Tyr705) proteins gradually decreased. After inhibiting miR-98-5p in the aluminum exposure group, the cell apoptosis rate and expression of apoptosis-related proteins decreased, and the expression of IGF2 mRNA and IGF2/JAK2/STAT3 proteins increased. These results indicate that miR-98-5p plays a vital role in aluminum-induced neurotoxicity by targeting IGF2.
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Affiliation(s)
- Chanting He
- Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China
- Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi 030001, China
- MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, China
- Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Qian Hu
- Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Congying Liu
- Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Yafen Chu
- Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jingjing Jia
- Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Xiaoyan Zhang
- Anesthesiology College, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Qiao Niu
- Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China
- Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi 030001, China
- MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, China
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Song G, Yu X, Shi H, Sun B, Amateau S. miRNAs in HCC, pathogenesis, and targets. Hepatology 2024:01515467-990000000-01097. [PMID: 39626210 PMCID: PMC12119976 DOI: 10.1097/hep.0000000000001177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/22/2024] [Indexed: 12/21/2024]
Abstract
Liver cancer is the third leading cause of cancer-related mortality worldwide. HCC, the most common type of primary liver cancer, is driven by complex genetic, epigenetic, and environmental factors. MicroRNAs, a class of naturally occurring small noncoding RNAs, play crucial roles in HCC by simultaneously modulating the expression of multiple genes in a fine-tuning manner. Significant progress has been made in understanding how miRNAs influence key oncogenic pathways, including cell proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT), as well as their role in modulating the immune microenvironment in HCC. Due to the unexpected stability of miRNAs in the blood and fixed HCC tumors, recent advancements also highlight their potential as noninvasive diagnostic tools. Restoring or inhibiting specific miRNAs has offered promising strategies for targeted HCC treatment by suppressing malignant hepatocyte growth and enhancing antitumor immunity. In this comprehensive review, we consolidate previous research and provide the latest insights into how miRNAs regulate HCC and their therapeutic and diagnostic potential. We delve into the dysregulation of miRNA biogenesis in HCC, the roles of miRNAs in the proliferation and apoptosis of malignant hepatocytes, angiogenesis and metastasis of HCC, the immune microenvironment in HCC, and drug resistance. We also discuss the therapeutic and diagnostic potential of miRNAs and delivery approaches of miRNA drugs to overcome the limitations of current HCC treatment options. By thoroughly summarizing the roles of miRNAs in HCC, our goal is to advance the development of effective therapeutic drugs with minimal adverse effects and to establish precise tools for early diagnosis of HCC.
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Affiliation(s)
- Guisheng Song
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
- Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA
| | - Xiaofan Yu
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Hongtao Shi
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
- Department of Cardiology, the First Hospital of Shanxi Medical University, Taiyuan City, China
| | - Bo Sun
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Stuart Amateau
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
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Fagoonee S, Weiskirchen R. MicroRNAs and RNA-Binding Protein-Based Regulation of Bone Metastasis from Hepatobiliary Cancers and Potential Therapeutic Strategies. Cells 2024; 13:1935. [PMID: 39682684 PMCID: PMC11640337 DOI: 10.3390/cells13231935] [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: 10/28/2024] [Revised: 11/15/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatobiliary cancers, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are among the deadliest malignancies worldwide, leading to a significant number of cancer-related deaths. While bone metastases from these cancers are rare, they are highly aggressive and linked to poor prognosis. This review focuses on RNA-based molecular mechanisms that contribute to bone metastasis from hepatobiliary cancers. Specifically, the role of two key factors, microRNAs (miRNAs) and RNA-binding proteins (RBPs), which have not been extensively studied in the context of HCC and CCA, is discussed. These molecules often exhibit abnormal expression in hepatobiliary tumors, influencing cancer cell spread and metastasis by disrupting bone homeostasis, thereby aiding tumor cell migration and survival in the bone microenvironment. This review also discusses potential therapeutic strategies targeting these RNA-based pathways to reduce bone metastasis and improve patient outcomes. Further research is crucial for developing effective miRNA- and RBP-based diagnostic and prognostic biomarkers and treatments to prevent bone metastases in hepatobiliary cancers.
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Affiliation(s)
- Sharmila Fagoonee
- Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center “Guido Tarone”, 10126 Turin, Italy
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany
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Carpi S, Daniele S, de Almeida JFM, Gabbia D. Recent Advances in miRNA-Based Therapy for MASLD/MASH and MASH-Associated HCC. Int J Mol Sci 2024; 25:12229. [PMID: 39596297 PMCID: PMC11595301 DOI: 10.3390/ijms252212229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 11/08/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a growing health concern worldwide, affecting more than 1 billion adults. It may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and ultimately hepatocellular carcinoma (HCC). Emerging evidence has demonstrated the role in this transition of microRNAs (miRNAs), which regulate the expression of genes associated with lipid metabolism, inflammation, fibrosis, and cell proliferation. Specific miRNAs have been identified to exacerbate or mitigate fibrotic and carcinogenic processes in hepatic cells. The modulation of these miRNAs through synthetic mimics or inhibitors represents a promising therapeutic strategy. Preclinical models have demonstrated that miRNA-based therapies can attenuate liver inflammation, reduce fibrosis, and inhibit tumorigenesis, thus delaying or preventing the onset of HCC. However, challenges such as delivery mechanisms, off-target effects, and long-term safety remain to be addressed. This review, focusing on recently published preclinical and clinical studies, explores the pharmacological potential of miRNA-based interventions to prevent MASLD/MASH and progression toward HCC.
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Affiliation(s)
- Sara Carpi
- Department of Health Sciences, University ‘Magna Græcia’ of Catanzaro, 88100 Catanzaro, Italy
- NEST (National Enterprise for nanoScience and nanoTechnology), Istituto Nanoscienze-CNR and Scuola Normale Superiore, 41125 Modena, Italy
| | - Simona Daniele
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy; (S.D.); (J.F.M.d.A.)
| | | | - Daniela Gabbia
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
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Fawzy MP, Hassan HAFM, Sedky NK, Nafie MS, Youness RA, Fahmy SA. Revolutionizing cancer therapy: nanoformulation of miRNA-34 - enhancing delivery and efficacy for various cancer immunotherapies: a review. NANOSCALE ADVANCES 2024:d4na00488d. [PMID: 39309515 PMCID: PMC11414826 DOI: 10.1039/d4na00488d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 09/12/2024] [Indexed: 09/25/2024]
Abstract
Despite recent advancements in cancer therapies, challenges such as severe toxic effects, non-selective targeting, resistance to chemotherapy and radiotherapy, and recurrence of metastatic tumors persist. Consequently, there has been considerable effort to explore innovative anticancer compounds, particularly in immunotherapy, which offer the potential for enhanced biosafety and efficacy in cancer prevention and treatment. One such avenue of exploration involves the miRNA-34 (miR-34) family, known for its ability to inhibit tumorigenesis across various cancers. Dysregulation of miR-34 has been observed in several human cancers, and it is recognized as a tumor suppressor microRNA due to its synergistic interaction with the well-established tumor suppressor p53. However, challenges have arisen with the therapeutic application of miR-34a. These include its susceptibility to degradation by RNase in serum, limiting its ability to penetrate capillary endothelium and reach target cells, as well as reports of immunoreactive adverse reactions. Furthermore, unexpected side effects may occur, such as the accumulation of therapeutic miRNAs in healthy tissues due to interactions with serum proteins on nano-vector surfaces, nanoparticle breakdown in the bloodstream due to shearing stress, and unsuccessful extravasation of nanocarriers to target cells owing to interstitial fluid pressure. Despite these challenges, miR-34a remains a promising candidate for cancer therapy, and other members of the miR-34 family have also shown potential in inhibiting tumor cell proliferation. While the in vivo applications of miR-34b/c are limited, they warrant further exploration for oncotherapy. Recently, procedures utilizing nanoparticles have been developed to address the challenges associated with the clinical use of miR-34, demonstrating efficacy both in vitro and in vivo. This review highlights emerging trends in nanodelivery systems for miR-34 targeting cancer cells, offering insights into novel nanoformulations designed to enhance the anticancer therapeutic activity and targeting precision of miR-34. As far as current knowledge extends, no similar recent review comprehensively addresses the diverse nanoformulations aimed at optimizing the therapeutic potential of miR-34 in anticancer strategies.
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Affiliation(s)
- Marola Paula Fawzy
- Department of Chemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation R5 New Garden City, New Capital Cairo 11835 Egypt
| | - Hatem A F M Hassan
- Medway School of Pharmacy, University of Kent Central Avenue, Chatham Maritime Canterbury ME44TB UK
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University 11562 Cairo 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
| | - Mohamed S Nafie
- Department of Chemistry, College of Sciences, University of Sharjah (P.O. 27272) Sharjah United Arab Emirates (UAE)
- Chemistry Department, Faculty of Science, Suez Canal University (P.O. 41522) Ismailia Egypt
| | - Rana A Youness
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU) 11835 Cairo Egypt
| | - 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 Capital Cairo 11835 Egypt
- Department of Pharmaceutics and Biopharmaceutics, University of Marburg Robert-Koch-Str. 4 35037 Marburg Germany
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Song H, Zhang Q, Fang G, Luo X, Wu D, Li H, Zhou K, Zhao X, Xu F, Zhang Y, Huang A. Unraveling the Mechanisms of MicroRNA in Suppressing Hepatitis B Virus Progression: A Comprehensive Review for Designing Treatment Strategies. HEPATITIS MONTHLY 2024; 24. [DOI: 10.5812/hepatmon-144239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 06/22/2024] [Accepted: 07/13/2024] [Indexed: 01/02/2025]
Abstract
: Liver cancer and cirrhosis caused by the Hepatitis B virus (HBV) remain significant global health challenges due to the virus's high prevalence and contagious nature. Hepatitis B virus can be transmitted through various means, leading to mild or severe liver disease. Although an effective prophylactic vaccine is available, it offers limited benefits for those already chronically infected. Current treatments often fail to consistently eliminate the virus and can cause severe adverse effects. In response to these challenges, researchers have begun exploring microRNAs (miRNAs) as novel therapeutic targets. Studying miRNA-virus interactions presents a promising opportunity to identify potential therapeutic targets. By manipulating host miRNAs, researchers aim to enhance antiviral defenses, restore cellular balance, and prevent viral replication. The text concludes by highlighting the potential for personalized medicine in Hepatitis B treatment, guided by individual miRNA profiles. Numerous studies have been conducted to understand how different miRNAs inhibit HBV replication, paving the way for the development of innovative and effective therapeutic strategies.
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Wang H. A Review of Nanotechnology in microRNA Detection and Drug Delivery. Cells 2024; 13:1277. [PMID: 39120308 PMCID: PMC11311607 DOI: 10.3390/cells13151277] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/27/2024] [Accepted: 07/28/2024] [Indexed: 08/10/2024] Open
Abstract
MicroRNAs (miRNAs) are small, non-coding RNAs that play a crucial role in regulating gene expression. Dysfunction in miRNAs can lead to various diseases, including cancers, neurological disorders, and cardiovascular conditions. To date, approximately 2000 miRNAs have been identified in humans. These small molecules have shown promise as disease biomarkers and potential therapeutic targets. Therefore, identifying miRNA biomarkers for diseases and developing effective miRNA drug delivery systems are essential. Nanotechnology offers promising new approaches to addressing scientific and medical challenges. Traditional miRNA detection methods include next-generation sequencing, microarrays, Northern blotting, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Nanotechnology can serve as an effective alternative to Northern blotting and RT-qPCR for miRNA detection. Moreover, nanomaterials exhibit unique properties that differ from larger counterparts, enabling miRNA therapeutics to more effectively enter target cells, reduce degradation in the bloodstream, and be released in specific tissues or cells. This paper reviews the application of nanotechnology in miRNA detection and drug delivery systems. Given that miRNA therapeutics are still in the developing stages, nanotechnology holds great promise for accelerating miRNA therapeutics development.
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Affiliation(s)
- Hsiuying Wang
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan
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Xue X, Li Y, Yao Y, Zhang S, Peng C, Li Y. A comprehensive review of miR-21 in liver disease: Big impact of little things. Int Immunopharmacol 2024; 134:112116. [PMID: 38696909 DOI: 10.1016/j.intimp.2024.112116] [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: 02/21/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 05/04/2024]
Abstract
microRNAs (miRNAs), a class of non-coding RNA with 20-24 nucleotides, are defined as the powerful regulators for gene expression. miR-21 is a multifunctional miRNA enriched in the circulatory system and multiple organs, which not only serves as a non-invasive biomarker in disease diagnosis, but also participates in many cellular activities. In various chronic liver diseases, the increase of miR-21 affects glycolipid metabolism, viral infection, inflammatory and immune cell activation, hepatic stellate cells activation and tissue fibrosis, and autophagy. Moreover, miR-21 is also a liaison in the deterioration of chronic liver disease to hepatocellular carcinoma (HCC), and it impacts on cell proliferation, apoptosis, migration, invasion, angiogenesis, immune escape, and epithelial-mesenchymal transformation by regulating target genes expression in different signaling pathways. In current research on miRNA therapy, some natural products can exert the hepatoprotective effects depending on the inhibition of miR-21 expression. In addition, miR-21-based therapeutic also play a role in regulating intracellular miR-21 levels and enhancing the efficacy of chemotherapy drugs. Herein, we systemically summarized the recent progress of miR-21 on biosynthesis, biomarker function, molecular mechanism and miRNA therapy in chronic liver disease and HCC, and looked forward to outputting some information to enable it from bench to bedside.
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Affiliation(s)
- Xinyan Xue
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yanzhi Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yuxin Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shenglin Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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Moaveni AK, Amiri M, Shademan B, Farhadi A, Behroozi J, Nourazarian A. Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update. Front Mol Biosci 2024; 11:1382190. [PMID: 38836106 PMCID: PMC11149429 DOI: 10.3389/fmolb.2024.1382190] [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: 02/05/2024] [Accepted: 03/27/2024] [Indexed: 06/06/2024] Open
Abstract
Pediatric cancers represent a tragic but also promising area for gene therapy. Although conventional treatments have improved survival rates, there is still a need for targeted and less toxic interventions. This article critically analyzes recent advances in gene therapy for pediatric malignancies and discusses the challenges that remain. We explore the innovative vectors and delivery systems that have emerged, such as adeno-associated viruses and non-viral platforms, which show promise in addressing the unique pathophysiology of pediatric tumors. Specifically, we examine the field of chimeric antigen receptor (CAR) T-cell therapies and their adaptation for solid tumors, which historically have been more challenging to treat than hematologic malignancies. We also discuss the genetic and epigenetic complexities inherent to pediatric cancers, such as tumor heterogeneity and the dynamic tumor microenvironment, which pose significant hurdles for gene therapy. Ethical considerations specific to pediatric populations, including consent and long-term follow-up, are also analyzed. Additionally, we scrutinize the translation of research from preclinical models that often fail to mimic pediatric cancer biology to the regulatory landscapes that can either support or hinder innovation. In summary, this article provides an up-to-date overview of gene therapy in pediatric oncology, highlighting both the rapid scientific progress and the substantial obstacles that need to be addressed. Through this lens, we propose a roadmap for future research that prioritizes the safety, efficacy, and complex ethical considerations involved in treating pediatric patients. Our ultimate goal is to move from incremental advancements to transformative therapies.
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Affiliation(s)
- Amir Kian Moaveni
- Pediatric Urology and Regenerative Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Amiri
- Pediatric Urology and Regenerative Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Behrouz Shademan
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Arezoo Farhadi
- Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Javad Behroozi
- Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Alireza Nourazarian
- Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran
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12
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Chen Y, Song Y, Zhu X, Dong CM, Chen M. Design and Update of Multifunctional Polypeptides and Their Applications for the Prevention of Viral Infections and Cancer Immunotherapies. POLYM REV 2024; 64:528-574. [DOI: 10.1080/15583724.2023.2281462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 10/07/2023] [Accepted: 11/04/2023] [Indexed: 01/06/2025]
Affiliation(s)
- Yanzheng Chen
- School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Yingying Song
- School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Xinyuan Zhu
- School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Chang-Ming Dong
- School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Mingsheng Chen
- Shanghai Public Health Clinic Center, Fudan University, Shanghai, P. R. China
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13
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Lv Y, Sun X. Role of miRNA in pathogenesis, diagnosis, and prognosis in hepatocellular carcinoma. Chem Biol Drug Des 2024; 103:e14352. [PMID: 37726253 DOI: 10.1111/cbdd.14352] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/27/2023] [Accepted: 09/04/2023] [Indexed: 09/21/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and is responsible for the second cancer-related death globally. Many treatment regimens have been developed to cure the disease; however, life expectancy is still low. Therefore, there is an urgent need to explore new selective, specific, and robust diagnosis markers for efficient early recognition of the ailment. Along with the diagnosis, the treatment's effectiveness can be determined by prognostic markers, and miRNAs are excellent tools for the diagnosis and prognosis of HCC. In addition, the altered expression profile of a few miRNAs promotes HCC cell migration and invasion, and selective up- or downregulation of these responsible genes may help mitigate the disorder. On one hand, few of the miRNAs have been found to enhance angiogenesis, a crucial step of tumor growth; on the other hand, upregulation of specific miRNAs is reported to suppress angiogenesis and resulting tumor growth of HCC cells. Exosomal miRNAs have significant implications in promoting angiogenesis, increased endothelial cell permeability, tube formation, and metastasis to hepatic and pulmonary tissues. miRNA also attributes to drug resistance toward chemotherapy and the prevention of autophagy also. Identifying novel miRNA and determining their differential expression in HCC tissue may serve as a potential tool for diagnosis, prognosis, and therapy to enhance the life expectancy and quality of life of HCC patients. In the present review, we have summarized the recent advances in HCC-related research.
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Affiliation(s)
- Yi Lv
- Hepatobiliary and Pancreatic Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi, China
| | - Xiujuan Sun
- Department of Pathology, Liuzhou People's Hospital, Liuzhou, Guangxi, China
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14
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Yerukala Sathipati S, Aimalla N, Tsai MJ, Carter T, Jeong S, Wen Z, Shukla SK, Sharma R, Ho SY. Prognostic microRNA signature for estimating survival in patients with hepatocellular carcinoma. Carcinogenesis 2023; 44:650-661. [PMID: 37701974 DOI: 10.1093/carcin/bgad062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/01/2023] [Accepted: 09/08/2023] [Indexed: 09/14/2023] Open
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is one of the leading cancer types with increasing annual incidence and high mortality in the USA. MicroRNAs (miRNAs) have emerged as valuable prognostic indicators in cancer patients. To identify a miRNA signature predictive of survival in patients with HCC, we developed a machine learning-based HCC survival estimation method, HCCse, using the miRNA expression profiles of 122 patients with HCC. METHODS The HCCse method was designed using an optimal feature selection algorithm incorporated with support vector regression. RESULTS HCCse identified a robust miRNA signature consisting of 32 miRNAs and obtained a mean correlation coefficient (R) and mean absolute error (MAE) of 0.87 ± 0.02 and 0.73 years between the actual and estimated survival times of patients with HCC; and the jackknife test achieved an R and MAE of 0.73 and 0.97 years between actual and estimated survival times, respectively. The identified signature has seven prognostic miRNAs (hsa-miR-146a-3p, hsa-miR-200a-3p, hsa-miR-652-3p, hsa-miR-34a-3p, hsa-miR-132-5p, hsa-miR-1301-3p and hsa-miR-374b-3p) and four diagnostic miRNAs (hsa-miR-1301-3p, hsa-miR-17-5p, hsa-miR-34a-3p and hsa-miR-200a-3p). Notably, three of these miRNAs, hsa-miR-200a-3p, hsa-miR-1301-3p and hsa-miR-17-5p, also displayed association with tumor stage, further emphasizing their clinical relevance. Furthermore, we performed pathway enrichment analysis and found that the target genes of the identified miRNA signature were significantly enriched in the hepatitis B pathway, suggesting its potential involvement in HCC pathogenesis. CONCLUSIONS Our study developed HCCse, a machine learning-based method, to predict survival in HCC patients using miRNA expression profiles. We identified a robust miRNA signature of 32 miRNAs with prognostic and diagnostic value, highlighting their clinical relevance in HCC management and potential involvement in HCC pathogenesis.
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Affiliation(s)
| | - Nikhila Aimalla
- Department of Internal Medicine-Pediatrics, Marshfield Clinic Health System, Marshfield, WI 54449, USA
| | - Ming-Ju Tsai
- Hinda and Arthur Marcus Institute for Aging Research at Hebrew Senior Life, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Tonia Carter
- Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI 54449, USA
| | - Sohyun Jeong
- Hinda and Arthur Marcus Institute for Aging Research at Hebrew Senior Life, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Zhi Wen
- Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI 54449, USA
| | - Sanjay K Shukla
- Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI 54449, USA
| | - Rohit Sharma
- Department of Surgical Oncology, Marshfield Clinic Health System, Marshfield, WI 54449, USA
| | - Shinn-Ying Ho
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
- Biomedical Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
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15
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Zhou M, He X, Mei C, Ou C. Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers. Biomark Res 2023; 11:100. [PMID: 37981718 PMCID: PMC10658727 DOI: 10.1186/s40364-023-00538-w] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 11/05/2023] [Indexed: 11/21/2023] Open
Abstract
Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50-150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.
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Affiliation(s)
- Manli Zhou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoyun He
- Departments of Ultrasound Imaging, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Cheng Mei
- Department of Blood Transfusion, Xiangya Hospital, Clinical Transfusion Research Center, Central South University, Changsha, 410008, Hunan, China.
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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16
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Rafieenia F, Ebrahimi SO, Emadi ES, Taheri F, Reiisi S. Bioengineered chimeric tRNA/pre-miRNAs as prodrugs in cancer therapy. Biotechnol Prog 2023; 39:e3387. [PMID: 37608520 DOI: 10.1002/btpr.3387] [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: 07/06/2023] [Revised: 08/08/2023] [Accepted: 08/09/2023] [Indexed: 08/24/2023]
Abstract
Today, biologic prodrugs have led to targeting specific tumor markers and have increased specificity and selectivity in cancer therapy. Various studies have shown the role of ncRNAs in cancer pathology and tumorigenesis and have suggested that ncRNAs, especially miRNAs, are valuable molecules in understanding cancer biology and therapeutic processes. Most miRNAs-based research and treatment are limited to chemically synthesized miRNAs. Synthetic alterations in these miRNA mimics may affect their folding, safety profile, and even biological activity. However, despite synthetic miRNA mimics produced by automated systems, various carriers could be used to achieve efficient production of bioengineered miRNAs through economical microbial fermentation. These bioengineered miRNAs as biological prodrugs could provide a new approach for safe therapeutic methods and drug production. In this regard, bioengineered chimeric miRNAs could be selectively processed to mature miRNAs in different types of cancer cells by targeting the desired gene and regulating cancer progression. In this article, we aim to review bioengineered miRNAs and their use in cancer therapy, as well as offering advances in this area, including the use of chimeric tRNA/pre-miRNAs.
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Affiliation(s)
- Fatemeh Rafieenia
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Seyed Omar Ebrahimi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Ensieh Sadat Emadi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Forough Taheri
- Department of Genetics, Sharekord Branch, Islamic Azad University, Sharekord
| | - Somayeh Reiisi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
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17
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Ren X, Su D, Shi D, Xiang X. The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment. Front Bioeng Biotechnol 2023; 11:1272850. [PMID: 37811369 PMCID: PMC10557528 DOI: 10.3389/fbioe.2023.1272850] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/08/2023] [Indexed: 10/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death worldwide. Conventional treatments for HCC include drugs, radiation, and surgery. Despite the unremitting efforts of researchers, the curative effect of HCC has been greatly improved, but because HCC is often found in the middle and late stages, the curative effect is still not satisfactory, and the 5-year survival rate is still low. Nanomedicine is a potential subject, which has been applied to the treatment of HCC and has achieved promising results. Here, we summarized the factors affecting the efficacy of drugs in HCC treatment and the strategies for improving the efficacy of nanotechnology-based drugs in HCC, reviewed the recent applications' progress on nanotechnology-based drugs in HCC treatment, and discussed the future perspectives and challenges of nanotechnology-based drugs in HCC treatment.
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Affiliation(s)
- Xiangyang Ren
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Danyang Su
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Doudou Shi
- The Ninth Hospital of Xi’an, Xi’an, Shaanxi, China
| | - Xiaohong Xiang
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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18
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Shahraki K, Boroumand PG, Lotfi H, Radnia F, Shahriari H, Sargazi S, Mortazavi SS, Shirvaliloo M, Shirvalilou S, Sheervalilou R. An update in the applications of exosomes in cancer theranostics: from research to clinical trials. J Cancer Res Clin Oncol 2023; 149:8087-8116. [PMID: 37010586 DOI: 10.1007/s00432-023-04701-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/17/2023] [Indexed: 04/04/2023]
Abstract
Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body.
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Affiliation(s)
- Kourosh Shahraki
- Department of Ophthalmology, Alzahra Eye Hospital, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Paria Ghasemi Boroumand
- ENT-Head and Neck Surgery Research Center and Department, Rasool Akram Hospital, Iran University of Medical Science, Tehran, Iran
| | - Hajie Lotfi
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Fatemeh Radnia
- Department of Medical Biotechnology, Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Shahriari
- Department of Immunology, School of Medicine, Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Milad Shirvaliloo
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Future Science Group, Unitec House, 2 Albert Place, London, N3 1QB, UK
| | - Sakine Shirvalilou
- Finetech in Medicine Research Center, Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Roghayeh Sheervalilou
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
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19
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Bravo-Vázquez LA, Méndez-García A, Rodríguez AL, Sahare P, Pathak S, Banerjee A, Duttaroy AK, Paul S. Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives. Front Bioeng Biotechnol 2023; 11:1208547. [PMID: 37576994 PMCID: PMC10416113 DOI: 10.3389/fbioe.2023.1208547] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 07/18/2023] [Indexed: 08/15/2023] Open
Abstract
MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease management strategy. However, over the past decade, artificial miRNAs (i.e., anti-miRNAs and miRNA mimics) have shown promising results against various cancer types; nevertheless, their targeted delivery could be challenging. Notably, numerous reports have shown that nanotechnology-based delivery of miRNAs can greatly contribute to hindering cancer initiation and development processes, representing an innovative disease-modifying strategy against cancer. Hence, in this review, we evaluate recently developed nanotechnology-based miRNA drug delivery systems for cancer therapeutics and discuss the potential challenges and future directions, such as the promising use of plant-made nanoparticles, phytochemical-mediated modulation of miRNAs, and nanozymes.
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Affiliation(s)
| | | | - Alma L. Rodríguez
- Tecnologico de Monterrey, School of Engineering and Sciences, Querétaro, México
| | - Padmavati Sahare
- Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Asim K. Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Querétaro, México
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20
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Minjares M, Wu W, Wang JM. Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders. Cells 2023; 12:1341. [PMID: 37174741 PMCID: PMC10177439 DOI: 10.3390/cells12091341] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/28/2023] [Accepted: 05/06/2023] [Indexed: 05/15/2023] Open
Abstract
Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced dysfunction, and the current knowledge of common metabolic disorders and their connection to oxidative stress. Therapeutic strategies based on microRNAs in response to oxidative stress and microRNA's regulatory roles in controlling ROS will also be explored. It is important to gain an in-depth comprehension of the mechanisms generating ROS and how manipulating these enzymatic byproducts can protect endothelial cell function from oxidative stress and prevent the development of vascular disorders.
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Affiliation(s)
- Morgan Minjares
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA;
| | - Wendy Wu
- Vera P Shiffman Medical Library, Wayne State University, 320 E Canfield St., Detroit, MI 48201, USA;
| | - Jie-Mei Wang
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA;
- Center for Molecular Medicine and Genetics, Wayne State University, 320 E Canfield St., Detroit, MI 48201, USA
- Barbara Ann Karmanos Cancer Institute, 4100 John R St., Detroit, MI 48201, USA
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21
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Hu X, Zhu H, He X, Chen J, Xiong L, Shen Y, Li J, Xu Y, Chen W, Liu X, Cao D, Xu X. The application of nanoparticles in immunotherapy for hepatocellular carcinoma. J Control Release 2023; 355:85-108. [PMID: 36708880 DOI: 10.1016/j.jconrel.2023.01.051] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/30/2023]
Abstract
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, however, current clinical diagnostic and treatment approaches remain relatively limited, creating an urgent need for the development of effective technologies. Immunotherapy has emerged as a powerful treatment strategy for advanced cancer. The number of clinically approved drugs for HCC immunotherapy has been increasing. However, it remains challenging to improve their transport and therapeutic efficiency, control their targeting and release, and mitigate their adverse effects. Nanotechnology has recently gained attention for improving the effectiveness of precision therapy for HCC. We summarize the key features of HCC associated with nanoparticle (NPs) targeting, release, and uptake, the roles and limitations of several major immunotherapies in HCC, the use of NPs in immunotherapy, the properties of NPs that influence their design and application, and current clinical trials of NPs in HCC, with the aim of informing the design of delivery platforms that have the potential to improve the safety and efficacy of HCC immunotherapy，and thus, ultimately improve the prognosis of HCC patients.
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Affiliation(s)
- Xinyao Hu
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Hua Zhu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Xiaoqin He
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Jiayu Chen
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Lin Xiong
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Yang Shen
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Jiayi Li
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Yangtao Xu
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Wenliang Chen
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Xin Liu
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Dedong Cao
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
| | - Ximing Xu
- Cancer center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
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22
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Tumor vasculature VS tumor cell targeting: Understanding the latest trends in using functional nanoparticles for cancer treatment. OPENNANO 2023. [DOI: 10.1016/j.onano.2023.100136] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
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23
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Sukocheva OA, Liu J, Neganova ME, Beeraka NM, Aleksandrova YR, Manogaran P, Grigorevskikh EM, Chubarev VN, Fan R. Perspectives of using microRNA-loaded nanocarriers for epigenetic reprogramming of drug resistant colorectal cancers. Semin Cancer Biol 2022; 86:358-375. [PMID: 35623562 DOI: 10.1016/j.semcancer.2022.05.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 02/07/2023]
Abstract
Epigenetic regulation by microRNAs (miRs) demonstrated a promising therapeutic potential of these molecules to regulate genetic activity in different cancers, including colorectal cancers (CRCs). The RNA-based therapy does not change genetic codes in tumor cells but can silence oncogenes and/or reactivate inhibited tumor suppressor genes. In many cancers, specific miRs were shown to promote or stop tumor progression. Among confirmed and powerful epigenetic regulators of colon carcinogenesis and development of resistance are onco-miRs, which include let-7, miR-21, miR-22, miR-23a, miR-27a, miR-34, miR-92, miR-96, miR-125b, miR-135b, miR-182, miR-200c, miR-203, miR-221, miR-421, miR-451, and others. Moreover, various tumor-suppressor miRs (miR-15b-5b, miR-18a, miR-20b, miR-22, miR-96, miR-139-5p, miR-145, miR-149, miR-197, miR-199b, miR-203, miR-214, miR-218, miR-320, miR-375-3p, miR-409-3p, miR-450b-5p, miR-494, miR-577, miR-874, and others) were found silenced in drug-resistant CRCs. Re-expression of tumor suppressor miR is complicated by the chemical nature of miRs that are not long-lasting compounds and require protection from the enzymatic degradation. Several recent studies explored application of miRs using nanocarrier complexes. This study critically describes the most successfully tested nanoparticle complexes used for intracellular delivery of nuclear acids and miRs, including micelles, liposomes, inorganic and polymeric NPs, dendrimers, and aptamers. Nanocarriers shield incorporated miRs and improve the agent stability in circulation. Attachment of antibodies and/or specific peptide or ligands facilitates cell-targeted miR delivery. Addressing in vivo challenges, a broad spectrum of non-toxic materials has been tested and indicated reliable advantages of lipid-based (lipoplexes) and polymer-based liposomes. Recent cutting-edge developments indicated that lipid-based complexes with multiple cargo, including several miRs, are the most effective approach to eradicate drug-resistant tumors. Focusing on CRC-specific miRs, this review provides a guidance and insights towards the most promising direction to achieve dramatic reduction in tumor growth and metastasis using miR-nanocarrier complexes.
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Affiliation(s)
- Olga A Sukocheva
- Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China; The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Queensland, Australia; Discipline of Health Sciences, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia.
| | - Junqi Liu
- Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China
| | - Margarita E Neganova
- Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1, Severnii pr., Chernogolovka 142432, Russia
| | - Narasimha M Beeraka
- Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China; Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow 119991, Russia; Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), JSS Medical College, Mysuru, Karnataka, India
| | - Yulia R Aleksandrova
- Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1, Severnii pr., Chernogolovka 142432, Russia
| | - Prasath Manogaran
- Translational Research Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641046, India
| | - Ekaterina M Grigorevskikh
- Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow 119991, Russia
| | - Vladimir N Chubarev
- Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow 119991, Russia
| | - Ruitai Fan
- Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China.
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Abedi-Gaballu F, Kamal Kazemi E, Salehzadeh SA, Mansoori B, Eslami F, Emami A, Dehghan G, Baradaran B, Mansoori B, Cho WC. Metabolic Pathways in Breast Cancer Reprograming: An Insight to Non-Coding RNAs. Cells 2022; 11:2973. [PMID: 36230935 PMCID: PMC9563138 DOI: 10.3390/cells11192973] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/10/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Cancer cells reprogram their metabolisms to achieve high energetic requirements and produce precursors that facilitate uncontrolled cell proliferation. Metabolic reprograming involves not only the dysregulation in glucose-metabolizing regulatory enzymes, but also the enzymes engaging in the lipid and amino acid metabolisms. Nevertheless, the underlying regulatory mechanisms of reprograming are not fully understood. Non-coding RNAs (ncRNAs) as functional RNA molecules cannot translate into proteins, but they do play a regulatory role in gene expression. Moreover, ncRNAs have been demonstrated to be implicated in the metabolic modulations in breast cancer (BC) by regulating the metabolic-related enzymes. Here, we will focus on the regulatory involvement of ncRNAs (microRNA, circular RNA and long ncRNA) in BC metabolism, including glucose, lipid and glutamine metabolism. Investigation of this aspect may not only alter the approaches of BC diagnosis and prognosis, but may also open a new avenue in using ncRNA-based therapeutics for BC treatment by targeting different metabolic pathways.
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Affiliation(s)
- Fereydoon Abedi-Gaballu
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz 51666-16471, Iran
| | - Elham Kamal Kazemi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz 51666-16471, Iran
| | - Seyed Ahmad Salehzadeh
- Department of Medicinal Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 175-14115, Iran
| | - Behnaz Mansoori
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 175-14115, Iran
| | - Farhad Eslami
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz 51666-16471, Iran
| | - Ali Emami
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz 51666-16471, Iran
| | - Gholamreza Dehghan
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz 51666-16471, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
| | - Behzad Mansoori
- Cellular and Molecular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
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25
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Gjorgjieva M, Ay AS, Correia de Sousa M, Delangre E, Dolicka D, Sobolewski C, Maeder C, Fournier M, Sempoux C, Foti M. MiR-22 Deficiency Fosters Hepatocellular Carcinoma Development in Fatty Liver. Cells 2022; 11:cells11182860. [PMID: 36139435 PMCID: PMC9496902 DOI: 10.3390/cells11182860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/02/2022] [Accepted: 09/09/2022] [Indexed: 12/24/2022] Open
Abstract
MiR-22 is mostly considered as a hepatic tumor-suppressor microRNA based on in vitro analyses. Yet, whether miR-22 exerts a tumor-suppressive function in the liver has not been investigated in vivo. Herein, in silico analyses of miR-22 expression were performed in hepatocellular carcinomas from human patient cohorts and different mouse models. Diethylnitrosamine-induced hepatocellular carcinomas were then investigated in lean and diet-induced obese miR-22-deficient mice. The proteome of liver tissues from miR-22-deficient mice prior to hepatocellular carcinoma development was further analyzed to uncover miR-22 regulated factors that impact hepatocarcinogenesis with miR-22 deficiency. MiR-22 downregulation was consistently observed in hepatocellular carcinomas from all human cohorts and mouse models investigated. The time of appearance of the first tumors was decreased and the number of tumoral foci induced by diethylnitrosamine was significantly increased by miR-22-deficiency in vivo, two features which were further drastically exacerbated with diet-induced obesity. At the molecular level, we provide evidence that the loss of miR-22 significantly affects the energetic metabolism and mitochondrial functions of hepatocytes, and the expression of tumor-promoting factors such as thrombospondin-1. Our study demonstrates that miR-22 acts as a hepatic tumor suppressor in vivo by restraining pro-carcinogenic metabolic deregulations through pleiotropic mechanisms and the overexpression of relevant oncogenes.
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Affiliation(s)
- Monika Gjorgjieva
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Anne-Sophie Ay
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Marta Correia de Sousa
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Etienne Delangre
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Dobrochna Dolicka
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Cyril Sobolewski
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Christine Maeder
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Margot Fournier
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
| | - Christine Sempoux
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
| | - Michelangelo Foti
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
- Translational Research Centre in Onco-Haematology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
- Correspondence:
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Zhou Y, Liu F, Ma C, Cheng Q. Involvement of microRNAs and their potential diagnostic, therapeutic, and prognostic role in hepatocellular carcinoma. J Clin Lab Anal 2022; 36:e24673. [PMID: 36036748 PMCID: PMC9551129 DOI: 10.1002/jcla.24673] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 07/01/2022] [Accepted: 08/13/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for 85%-90% of primary liver cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'UTR of mRNA. Abnormal expression and regulation of miRNAs are involved in the occurrence and progression of HCC, and miRNAs can also play a role in the diagnosis and treatment of HCC as oncogenes or tumor suppressors. METHODS In the past decades, a large number of studies have shown that miRNAs play an essential regulatory role in HCC and have potential as biomarkers for HCC. We reviewed the literature to summarize these studies. RESULTS By reviewing the literature, we retrospected the roles of miRNAs in the development, diagnosis, treatment, and prognosis of HCC, and put forward prospects for the further research on miRNAs in the precision treatment of HCC. CONCLUSION MicroRNAs are important regulators and biomarkers in the occurrence, progression, outcome, and treatment of HCC, and can provide new targets and strategies for improving the therapeutic effect of HCC.
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Affiliation(s)
- Yilong Zhou
- Department of Surgery, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Fan Liu
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China
| | - Chunyang Ma
- Department of Surgery, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Qiong Cheng
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, China
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27
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Sargazi S, Siddiqui B, Qindeel M, Rahdar A, Bilal M, Behzadmehr R, Mirinejad S, Pandey S. Chitosan nanocarriers for microRNA delivery and detection: A preliminary review with emphasis on cancer. Carbohydr Polym 2022; 290:119489. [DOI: 10.1016/j.carbpol.2022.119489] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 04/04/2022] [Accepted: 04/12/2022] [Indexed: 02/08/2023]
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Zhang CY, Liu S, Yang M. Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy. World J Gastroenterol 2022; 28:3346-3358. [PMID: 36158267 PMCID: PMC9346458 DOI: 10.3748/wjg.v28.i27.3346] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 01/27/2022] [Accepted: 06/23/2022] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is the third leading cause of cancer-related death worldwide with primary type hepatocellular carcinoma (HCC). Factors, including carcinogens, infection of hepatitis viruses, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD), can induce HCC initiation and promote HCC progression. The prevalence of NAFLD accompanying the increased incidence of obesity and type 2 diabetes becomes the most increasing factor causing HCC worldwide. However, the benefit of current therapeutic options is still limited. Intrahepatic immunity plays critically important roles in HCC initiation, development, and progression. Regulatory T cells (Tregs) and their associated factors such as metabolites and secreting cytokines mediate the immune tolerance of the tumor microenvironment in HCC. Therefore, targeting Tregs and blocking their mediated factors may prevent HCC progression. This review summarizes the functions of Tregs in HCC-inducing factors including alcoholic and NAFLD, liver fibrosis, cirrhosis, and viral infections. Overall, a better understanding of the role of Tregs in the development and progression of HCC provides treatment strategies for liver cancer treatment.
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Affiliation(s)
- Chun-Ye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, United States
| | - Shuai Liu
- The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65211, United States
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29
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Zhang C, Liu N. Noncoding RNAs in the Glycolysis of Ovarian Cancer. Front Pharmacol 2022; 13:855488. [PMID: 35431949 PMCID: PMC9005897 DOI: 10.3389/fphar.2022.855488] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 03/15/2022] [Indexed: 01/11/2023] Open
Abstract
Energy metabolism reprogramming is the characteristic feature of tumors. The tumorigenesis, metastasis, and drug resistance of ovarian cancer (OC) is dependent on energy metabolism. Even under adequate oxygen conditions, OC cells tend to convert glucose to lactate, and glycolysis can rapidly produce ATP to meet their metabolic energy needs. Non-coding RNAs (ncRNAs) interact directly with DNA, RNA, and proteins to function as an essential regulatory in gene expression and tumor pathology. Studies have shown that ncRNAs regulate the process of glycolysis by interacting with the predominant glycolysis enzyme and cellular signaling pathway, participating in tumorigenesis and progression. This review summarizes the mechanism of ncRNAs regulation in glycolysis in OC and investigates potential therapeutic targets.
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Affiliation(s)
- Chunmei Zhang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ning Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
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30
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El-Mahdy HA, Sallam AAM, Ismail A, Elkhawaga SY, Elrebehy MA, Doghish AS. miRNAs inspirations in hepatocellular carcinoma: Detrimental and favorable aspects of key performers. Pathol Res Pract 2022; 233:153886. [PMID: 35405621 DOI: 10.1016/j.prp.2022.153886] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/23/2022] [Accepted: 04/01/2022] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. HCC initiation, progression, and therapy failure are all influenced by various variables, including microRNAs (miRNAs). miRNAs are short non-coding RNA sequences that modulate target mRNA expression by deteriorating or repressing translation. miRNAs play an imperative role in HCC pathogenesis by triggering the induction of cancer stem cells (CSCs) and their proliferation, while also delaying apoptosis, sustaining the cell cycle, and inspiring angiogenesis, invasion, and metastasis. Additionally, miRNAs modulate crucial HCC-related molecular pathways such as the p53 pathway, the Wnt/β-catenin pathway, VEGFR2, and PTEN/PI3K/AKT pathway. Consequently, the goal of this review was to give an up-to-date overview of oncogenic and tumor suppressor (TS) miRNAs, as well as their potential significance in HCC pathogenesis and treatment responses, highlighting their underpinning molecular pathways in HCC initiation and progression. Similarly, the biological importance and clinical application of miRNAs in HCC are summarized.
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Affiliation(s)
- Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Al-Aliaa M Sallam
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Samy Y Elkhawaga
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
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Affiliation(s)
- Afsar Raza Naqvi
- College of Dentistry, University of Illinois, 801 S. Paulina St., Chicago, IL 60612, United States.
| | - Maryam Sarwat
- Amity Institute of Pharmacy, Amity University, Noida 201313, Uttar Pradesh, India.
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32
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Cannito S, Bincoletto V, Turato C, Pontisso P, Scupoli MT, Ailuno G, Andreana I, Stella B, Arpicco S, Bocca C. Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells. Molecules 2022; 27:molecules27031062. [PMID: 35164326 PMCID: PMC8840578 DOI: 10.3390/molecules27031062] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/26/2022] [Accepted: 02/01/2022] [Indexed: 11/30/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and is characterized by poor clinical outcomes, with the majority of patients not being eligible for curative therapy and treatments only being applicable for early-stage tumors. CD44 is a receptor for hyaluronic acid (HA) and is involved in HCC progression. The aim of this work is to propose HA- and PEGylated-liposomes as promising approaches for the treatment of HCC. It has been found, in this work, that CD44 transcripts are up-regulated in HCC patients, as well as in a murine model of NAFLD/NASH-related hepatocarcinogenesis. Cell culture experiments indicate that HA-liposomes are more rapidly and significantly internalized by Huh7 cells that over-express CD44, compared with HepG2 cells that express low levels of the receptor, in which the uptake seems due to endocytic events. By contrast, human and murine macrophage cell lines (THP-1, RAW264.7) show improved and rapid uptake of PEG-modified liposomes without the involvement of the CD44. Moreover, the internalization of PEG-modified liposomes seems to induce polarization of THP1 towards the M1 phenotype. In conclusion, data reported in this study indicate that this strategy can be proposed as an alternative for drug delivery and one that dually and specifically targets liver cancer cells and infiltrating tumor macrophages in order to counteract two crucial aspect of HCC progression.
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Affiliation(s)
- Stefania Cannito
- Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy; (S.C.); (C.B.)
| | - Valeria Bincoletto
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (V.B.); (I.A.); (B.S.)
| | - Cristian Turato
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy;
| | | | - Maria Teresa Scupoli
- Research Center LURM, Interdepartmental Laboratory of Medical Research, University of Verona, 37134 Verona, Italy;
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37129 Verona, Italy
| | - Giorgia Ailuno
- Department of Pharmacy, University of Genova, 16148 Genova, Italy;
| | - Ilaria Andreana
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (V.B.); (I.A.); (B.S.)
| | - Barbara Stella
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (V.B.); (I.A.); (B.S.)
| | - Silvia Arpicco
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (V.B.); (I.A.); (B.S.)
- Correspondence: ; Tel.: +39-011-670-6668
| | - Claudia Bocca
- Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy; (S.C.); (C.B.)
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Cione E, Cannataro R, Gallelli L, De Sarro G, Caroleo MC. Exosome microRNAs in Metabolic Syndrome as Tools for the Early Monitoring of Diabetes and Possible Therapeutic Options. Pharmaceuticals (Basel) 2021; 14:1257. [PMID: 34959658 PMCID: PMC8706321 DOI: 10.3390/ph14121257] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023] Open
Abstract
Exosomes are nano-sized extracellular vesicles produced and released by almost all cell types. They play an essential role in cell-cell communications by delivering cellular bioactive compounds such as functional proteins, metabolites, and nucleic acids, including microRNA, to recipient cells. Thus, they are involved in various physio-pathological conditions. Exosome-miRNAs are associated with numerous diseases, including type 2 diabetes, a complex multifactorial metabolic disorder linked to obesity. In addition, exosome-miRNAs are emerging as essential regulators in the progression of diabetes, principally for pancreatic β-cell injury and insulin resistance. Here, we have clustered the recent findings concerning exosome-miRNAs associated with β-cell dysfunction to provide a novel approach for the early diagnosis and therapy of diabetes.
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Affiliation(s)
- Erika Cione
- Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Ed. Polifunzionale, Arcavacata di Rende, 87036 Rende, CS, Italy;
- GalaScreen Laboratories, University of Calabria, Ed. Polifunzionale, Arcavacata di Rende, 87036 Rende, CS, Italy;
| | - Roberto Cannataro
- GalaScreen Laboratories, University of Calabria, Ed. Polifunzionale, Arcavacata di Rende, 87036 Rende, CS, Italy;
| | - Luca Gallelli
- Department of Health Science, University of Catanzaro and Operative Unit of Clinical Pharmacology and Pharmacovigilance, Mater Domini Hospital, 88100 Catanzaro, CZ, Italy; (L.G.); (G.D.S.)
| | - Giovambattista De Sarro
- Department of Health Science, University of Catanzaro and Operative Unit of Clinical Pharmacology and Pharmacovigilance, Mater Domini Hospital, 88100 Catanzaro, CZ, Italy; (L.G.); (G.D.S.)
| | - Maria Cristina Caroleo
- Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Ed. Polifunzionale, Arcavacata di Rende, 87036 Rende, CS, Italy;
- GalaScreen Laboratories, University of Calabria, Ed. Polifunzionale, Arcavacata di Rende, 87036 Rende, CS, Italy;
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Grabowska-Pyrzewicz W, Want A, Leszek J, Wojda U. Antisense oligonucleotides for Alzheimer's disease therapy: from the mRNA to miRNA paradigm. EBioMedicine 2021; 74:103691. [PMID: 34773891 PMCID: PMC8602003 DOI: 10.1016/j.ebiom.2021.103691] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 10/06/2021] [Accepted: 10/28/2021] [Indexed: 01/12/2023] Open
Abstract
Alzheimer's disease (AD) represents a particular therapeutic challenge because its aetiology is very complex, with dynamic progression from preclinical to clinical stages. Several potential therapeutic targets and strategies were tested for AD, in over 2000 clinical trials, but no disease-modifying therapy exists. This failure indicates that AD, as a multifactorial disease, may require multi-targeted approaches and the delivery of therapeutic molecules to the right place and at the right disease stage. Opportunities to meet the challenges of AD therapy appear to come from recent progress in knowledge and methodological advances in the design, synthesis, and targeting of brain mRNA and microRNA with synthetic antisense oligonucleotides (ASOs). Several types of ASOs allow the utilisation of different mechanisms of posttranscriptional regulation and offer enhanced effects over alternative therapeutics. This article reviews ASO-based approaches and targets in preclinical and clinical trials for AD, and presents the future perspective on ASO therapies for AD.
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Affiliation(s)
- Wioleta Grabowska-Pyrzewicz
- Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093, Warsaw, Poland
| | - Andrew Want
- Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093, Warsaw, Poland
| | - Jerzy Leszek
- Department of Psychiatry, Wroclaw Medical University, Wybrzeże Pasteura 10, 50-367 Wroclaw, Poland
| | - Urszula Wojda
- Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093, Warsaw, Poland.
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Li TT, Mou J, Pan YJ, Huo FC, Du WQ, Liang J, Wang Y, Zhang LS, Pei DS. MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated β-catenin/ABCB1 signaling pathway. J Biomed Sci 2021; 28:56. [PMID: 34340705 PMCID: PMC8327419 DOI: 10.1186/s12929-021-00752-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 07/20/2021] [Indexed: 12/19/2022] Open
Abstract
Background Sorafenib is a kinase inhibitor that is used as a first-line therapy in advanced hepatocellular carcinoma (HCC) patients. However, the existence of sorafenib resistance has limited its therapeutic effect. Through RNA sequencing, we demonstrated that miR-138-1-3p was downregulated in sorafenib resistant HCC cell lines. This study aimed to investigate the role of miR-138-1-3p in sorafenib resistance of HCC. Methods In this study, quantitative real-time PCR (qPCR) and Western Blot were utilized to detect the levels of PAK5 in sorafenib-resistant HCC cells and parental cells. The biological functions of miR-138-1-3p and PAK5 in sorafenib-resistant cells and their parental cells were explored by cell viability assays and flow cytometric analyses. The mechanisms for the involvement of PAK5 were examined via co-immunoprecipitation (co-IP), immunofluorescence, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). The effects of miR-138-1-3p and PAK5 on HCC sorafenib resistant characteristics were investigated by a xenotransplantation model. Results We detected significant down-regulation of miR-138-1-3p and up-regulation of PAK5 in sorafenib-resistance HCC cell lines. Mechanistic studies revealed that miR-138-1-3p reduced the protein expression of PAK5 by directly targeting the 3′-UTR of PAK5 mRNA. In addition, we verified that PAK5 enhanced the phosphorylation and nuclear translocation of β-catenin that increased the transcriptional activity of a multidrug resistance protein ABCB1. Conclusions PAK5 contributed to the sorafenib resistant characteristics of HCC via β-catenin/ABCB1 signaling pathway. Our findings identified the correlation between miR-138-1-3p and PAK5 and the molecular mechanisms of PAK5-mediated sorafenib resistance in HCC, which provided a potential therapeutic target in advanced HCC patients.
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Affiliation(s)
- Tong-Tong Li
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China.,Department of Pathology and Pathophysiology, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, China
| | - Jie Mou
- Jiangsu Key Laboratory of New Drug and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221006, China
| | - Yao-Jie Pan
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China
| | - Fu-Chun Huo
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China
| | - Wen-Qi Du
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China
| | - Jia Liang
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China
| | - Yang Wang
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China
| | - Lan-Sheng Zhang
- Department of Oncological Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
| | - Dong-Sheng Pei
- Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China.
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He X, Kuang G, Wu Y, Ou C. Emerging roles of exosomal miRNAs in diabetes mellitus. Clin Transl Med 2021; 11:e468. [PMID: 34185424 PMCID: PMC8236118 DOI: 10.1002/ctm2.468] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 06/01/2021] [Accepted: 06/07/2021] [Indexed: 12/14/2022] Open
Abstract
Exosomes are small extracellular vesicles 40-160 nm in diameter that are secreted by almost all cell types. Exosomes can carry diverse cargo including RNA, DNA, lipids, proteins, and metabolites. Exosomes transfer substances and information between cells by circulating in body fluids and are thus involved in diverse physiological and pathological processes in the human body. Recent studies have closely associated exosomal microRNAs (miRNAs) with various human diseases, including diabetes mellitus (DM), which is a complex multifactorial metabolic disorder disease. Exosomal miRNAs are emerging as pivotal regulators in the progression of DM, mainly in terms of pancreatic β-cell injury and insulin resistance. Exosomal miRNAs are closely associated with DM-associated complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic cardiomyopathy (DCM), etc. Further investigations of the mechanisms of action of exosomal miRNAs and their role in DM will be valuable for the thorough understanding of the physiopathological process of DM. Here, we have summarized recent findings regarding exosomal miRNAs associated with DM to provide a new strategy for identifying potential diagnostic biomarkers and drug targets for the early diagnosis and treatment, respectively, of DM.
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Affiliation(s)
- Xiaoyun He
- Department of Pathology, Xiangya HospitalCentral South UniversityChangshaHunan410008China
- Departments of Ultrasound Imaging, Xiangya HospitalCentral South UniversityChangshaHunan410008China
| | - Gaoyan Kuang
- Department of OrthopedicsThe First Affiliated Hospital of Hunan University of Chinese MedicineChangshaHunan410007China
- Postdoctoral Research WorkstationHinye Pharmaceutical Co. LtdChangshaHunan410331China
| | - Yongrong Wu
- Hunan university of Chinese MedicineChangshaHunan410208China
| | - Chunlin Ou
- Department of Pathology, Xiangya HospitalCentral South UniversityChangshaHunan410008China
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Cheng Z, Li M, Dey R, Chen Y. Nanomaterials for cancer therapy: current progress and perspectives. J Hematol Oncol 2021; 14:85. [PMID: 34059100 PMCID: PMC8165984 DOI: 10.1186/s13045-021-01096-0] [Citation(s) in RCA: 567] [Impact Index Per Article: 141.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/24/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer is a disease with complex pathological process. Current chemotherapy faces problems such as lack of specificity, cytotoxicity, induction of multi-drug resistance and stem-like cells growth. Nanomaterials are materials in the nanorange 1–100 nm which possess unique optical, magnetic, and electrical properties. Nanomaterials used in cancer therapy can be classified into several main categories. Targeting cancer cells, tumor microenvironment, and immune system, these nanomaterials have been modified for a wide range of cancer therapies to overcome toxicity and lack of specificity, enhance drug capacity as well as bioavailability. Although the number of studies has been increasing, the number of approved nano-drugs has not increased much over the years. To better improve clinical translation, further research is needed for targeted drug delivery by nano-carriers to reduce toxicity, enhance permeability and retention effects, and minimize the shielding effect of protein corona. This review summarizes novel nanomaterials fabricated in research and clinical use, discusses current limitations and obstacles that hinder the translation from research to clinical use, and provides suggestions for more efficient adoption of nanomaterials in cancer therapy.
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Affiliation(s)
- Zhe Cheng
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Maoyu Li
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Raja Dey
- Department of Nucleotide Metabolism and Drug Discovery, The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA
| | - Yongheng Chen
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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