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lncRNA ADAMTS9-AS2/let-7a-5p axis regulates metabolic reprogramming by targeting HK2 in oral submucous fibrosis-associated oral squamous cell carcinoma

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收录情况： ◇ 卓越：梯队期刊

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机构： [1]Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [2]College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China. [3]National Center for Stomatology, Shanghai 200011, China. [4]National Clinical Research Center for Oral Diseases, Shanghai 200011, China. [5]Shanghai Key Laboratory of Stomatology, Shanghai 200011, China. [6]Shanghai Research Institute of Stomatology, Shanghai 200011, China. [7]Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai 200011, China. [8]Center of Stomatology, Hainan West Central Hospital, Hainan 570105, China. [9]Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [10]Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [11]Department of Stomatology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [12]Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [13]Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

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关键词： ADAMTS9-AS2 Aerobic glycolysis HK2 let-7a-5p OSCC OSF

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Oral squamous cell carcinoma in the background of/with oral submucous fibrosis (OSCC-OSF) has a unique etiology and is clinically distinct from other OSCCs. We previously identified ADAMTS9-AS2 as a functional tumor suppressor in OSCC-OSF through the regulation of PI3K-AKT signaling. However, its role in metabolic modulation and the underlying mechanisms remain unclear. In this study, we reported for the first time that ADAMTS9-AS2 suppressed aerobic glycolysis by cooperating with let-7a-5p in OSCC cells. Mechanistically, let-7a-5p inhibited HK2 expression by targeting its 3'-UTR, further deregulating glycolytic function, while enhancing HK2 expression rescued the inhibitory effects of the ADAMTS9-AS2/let-7a-5p axis on aerobic glycolysis and OSCC cell growth. Exosomal ADAMTS9-AS2 regulated metabolic reprogramming during OSCC tumorigenesis. ABC transporters in lipid and pyrimidine metabolism were significantly enriched pathways. Changes in several key metabolites were identified after ADAMTS9-AS2 exosome treatment, including increased levels of DL-glutamic acid and D-mannose, along with decreased levels of cytidine and D-maltose. Thus, our findings demonstrate that ADAMTS9-AS2 drives let-7a-5p binding to HK2 to suppress cell growth in OSCC by abolishing aerobic glycolysis. Our data on metabolic reprogramming have greatly expanded the role of the ADAMTS9-AS2/let-7a-5p axis as a key regulator of metabolism during OSCC tumorigenesis.© 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltdé.

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出版当年[2025]版：

大类 | 2 区医学

小类 | 2 区生化与分子生物学 2 区遗传学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区生化与分子生物学 2 区遗传学

第一作者：

第一作者机构： [1]Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [2]College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China. [3]National Center for Stomatology, Shanghai 200011, China. [4]National Clinical Research Center for Oral Diseases, Shanghai 200011, China. [5]Shanghai Key Laboratory of Stomatology, Shanghai 200011, China. [6]Shanghai Research Institute of Stomatology, Shanghai 200011, China. [7]Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai 200011, China. [8]Center of Stomatology, Hainan West Central Hospital, Hainan 570105, China.

通讯作者：

通讯机构： [1]Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. [2]College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China. [3]National Center for Stomatology, Shanghai 200011, China. [4]National Clinical Research Center for Oral Diseases, Shanghai 200011, China. [5]Shanghai Key Laboratory of Stomatology, Shanghai 200011, China. [6]Shanghai Research Institute of Stomatology, Shanghai 200011, China. [7]Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai 200011, China. [8]Center of Stomatology, Hainan West Central Hospital, Hainan 570105, China.

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lncRNA ADAMTS9-AS2/let-7a-5p axis regulates metabolic reprogramming by targeting HK2 in oral submucous fibrosis-associated oral squamous cell carcinoma

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