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Small Activating RNA Modulation of the G Protein-Coupled Receptor for Cancer Treatment
Xiong, Yunfang1; Ke, Ran1; Zhang, Qingyu2; Lan, Wenjun3,4; Yuan, Wanjun1; Chan, Karol Nga Ieng1; Roussel, Tom3; Jiang, Yifan3; Wu, Jing3; Liu, Shuai1; Wong, Alice Sze Tsai5; Shim, Joong Sup1,6; Zhang, Xuanjun1,6; Xie, Ruiyu1,6; Dusetti, Nelson4; Iovanna, Juan4; Habib, Nagy7,8; Peng, Ling3; Lee, Leo Tsz On1,6,9
2022
Source PublicationAdvanced Science
ISSN2198-3844
Volume9Issue:26
Abstract

G protein-coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence-specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor-xenografted mouse models and patient-derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin-angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation.

KeywordCancer Therapies Dendrimer Vectors g Protein-coupled Receptors Mas Receptors (Mas1s) Small Activating Rna
DOI10.1002/advs.202200562
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS SubjectChemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000811991500001
Scopus ID2-s2.0-85131940983
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Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, 999078, Macao
2.Department of Obstetrics and Gynaecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China
3.Aix Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (UMR 7325), Equipe Labellisée Ligue Contre le Cancer, Marseille, 13288, France
4.Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS, Aix-Marseille Université and Institut Paoli-Calmettes, Marseille, 13288, France
5.School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong
6.MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, 999078, Macao
7.Department of Surgery and Cancer, Imperial College London, London, W12 0NN, United Kingdom
8.MiNA Therapeutics, Translation & Innovation Hub, London, 80 Wood Lane, W12 0BZ, United Kingdom
9.Centre of Reproduction, Development, and Aging, Faculty of Health Sciences, University of Macau, Taipa, 999078, Macao
First Author AffilicationCancer Centre
Recommended Citation
GB/T 7714
Xiong, Yunfang,Ke, Ran,Zhang, Qingyu,et al. Small Activating RNA Modulation of the G Protein-Coupled Receptor for Cancer Treatment[J]. Advanced Science,2022,9(26).
APA Xiong, Yunfang,Ke, Ran,Zhang, Qingyu,Lan, Wenjun,Yuan, Wanjun,Chan, Karol Nga Ieng,Roussel, Tom,Jiang, Yifan,Wu, Jing,Liu, Shuai,Wong, Alice Sze Tsai,Shim, Joong Sup,Zhang, Xuanjun,Xie, Ruiyu,Dusetti, Nelson,Iovanna, Juan,Habib, Nagy,Peng, Ling,&Lee, Leo Tsz On.(2022).Small Activating RNA Modulation of the G Protein-Coupled Receptor for Cancer Treatment.Advanced Science,9(26).
MLA Xiong, Yunfang,et al."Small Activating RNA Modulation of the G Protein-Coupled Receptor for Cancer Treatment".Advanced Science 9.26(2022).
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