Статья

TMEM64 aggravates the malignant phenotype of glioma by activating the Wnt/β-catenin signaling pathway

Hui YangAnhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, College of Life Sciences, Anhui Normal University, Wuhu 241001, Anhui, China; Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu 241001, Anhui, ChinaHanyu ZhouAnhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, ChinaMinjie FuDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, ChinaHao XuDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, ChinaHaoyu HuangAnhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, ChinaMin ZhongAnhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, ChinaMengying ZhangAnhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, ChinaWei HuaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China. Electronic address: [email protected]Kun LvAnhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, College of Life Sciences, Anhui Normal University, Wuhu 241001, Anhui, China; Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China. Electronic address: [email protected]Guoping ZhuAnhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, College of Life Sciences, Anhui Normal University, Wuhu 241001, Anhui, China; Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu 241001, Anhui, China. Electronic address: [email protected]

2024en

ABI

Аннотация

Transmembrane protein 64 (TMEM64), a member of the family of transmembrane protein, is an α-helical membrane protein. Its precise role in various types of tumors, including glioma, is unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher in glioma cells and tissues compared to normal cells and tissues, respectively. Additionally, a correlation between high TMEM64 expression and higher grade as well as a worse prognosis was found. TMEM64 enhanced cell proliferation and tumorigenicity while inhibiting glioma cell apoptosis in vitro and in vivo, according to loss- and gain-of-function studies. Mechanistically, it was discovered that TMEM64 increased the malignant phenotype of gliomas by accelerating the translocation of β-catenin from the cytoplasm to the nucleus, thereby activating the Wnt/β-catenin signaling pathway. Stimulation with the Wnt/β-catenin signaling pathway activator CHIR-99021 successfully reversed the malignant phenotype of glioma; however, these effects were inhibited upon TMEM64 silencing. Stimulation with the Wnt/β-catenin signaling pathway inhibitor XAV-939 successfully rescued the malignant phenotype of glioma, which was promoted upon TMEM64 overexpression. Our results provide that TMEM64 as a novel prognostic biomarker and a potential treatment target for glioma.

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Идентификаторы

DOI: 10.1016/j.ijbiomac.2024.129332

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Цитирований: 4Использованных источников: 0

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