Hongyan Yu1,2,3, Mingxu Xie1,2, Zhaoyue Meng1,2, Chun-Yin Lo1,2, Franky Leung Chan1, Liwen Jiang4, Xiangqi Meng5,6, Xiaoqiang Yao7,8,9. 1. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China. 2. Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China. 3. Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China. 4. Centre for Cell and Developmental Biology, State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China. 5. Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. mengxq3@mail.sysu.edu.cn. 6. Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. mengxq3@mail.sysu.edu.cn. 7. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China. yao2068@cuhk.edu.hk. 8. Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China. yao2068@cuhk.edu.hk. 9. Centre for Cell and Developmental Biology, State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China. yao2068@cuhk.edu.hk.
Abstract
BACKGROUND: Prostate cancer (Pca) is the most common cancer type among males worldwide. Dysregulation of Ca2+ signaling plays important roles during Pca progression. However, there is lack of information about the role of endolysosomal Ca2+ -permeable channels in Pca progression. METHODS: The expression pattern of MCOLN2 was studied by immunohistochemistry and western blot. Cell viability assay, transwell assay and in vivo tumorigenesis were performed to evaluate the functional role of MCOLN2. Downstream targets of MCOLN2 were investigated by cytokine array, enzyme-linked immunosorbent assay, Ca2+ release experiments and luciferase reporter assays. RESULTS: We report that MCOLN2 expression is significantly elevated in Pca tissues, and associated with poor prognosis. Overexpression of MCOLN2 promoted Pca cells proliferation, migration and invasion. Importantly, knockdown of MCOLN2 inhibited Pca xenograft tumor growth and bone lesion development in vivo. In addition, MCOLN2 promoted the production and release of IL-1β. Moreover, luciferase reporter assay and western blot revealed that MCOLN2 promoted Pca development by regulating the IL-1β/NF-κB pathway. CONCLUSION: In summary, MCOLN2 is crucially involved in Pca progression. Mechanistically, MCOLN2 regulates Pca progression via IL-1β/NF-κB pathway. Our study highlights an intriguing possibility of targeting MCOLN2 as potential therapeutic strategy in Pca treatment.
BACKGROUND: Prostate cancer (Pca) is the most common cancer type among males worldwide. Dysregulation of Ca2+ signaling plays important roles during Pca progression. However, there is lack of information about the role of endolysosomal Ca2+ -permeable channels in Pca progression. METHODS: The expression pattern of MCOLN2 was studied by immunohistochemistry and western blot. Cell viability assay, transwell assay and in vivo tumorigenesis were performed to evaluate the functional role of MCOLN2. Downstream targets of MCOLN2 were investigated by cytokine array, enzyme-linked immunosorbent assay, Ca2+ release experiments and luciferase reporter assays. RESULTS: We report that MCOLN2 expression is significantly elevated in Pca tissues, and associated with poor prognosis. Overexpression of MCOLN2 promoted Pca cells proliferation, migration and invasion. Importantly, knockdown of MCOLN2 inhibited Pca xenograft tumor growth and bone lesion development in vivo. In addition, MCOLN2 promoted the production and release of IL-1β. Moreover, luciferase reporter assay and western blot revealed that MCOLN2 promoted Pca development by regulating the IL-1β/NF-κB pathway. CONCLUSION: In summary, MCOLN2 is crucially involved in Pca progression. Mechanistically, MCOLN2 regulates Pca progression via IL-1β/NF-κB pathway. Our study highlights an intriguing possibility of targeting MCOLN2 as potential therapeutic strategy in Pca treatment.
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