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The target relationship between SPI1 and hexokinase 2 (HK2) was determined using dual\u2010luciferase reporter detection. ChIP was conducted to confirm the targeted relationship between SPI1 and the HK2 promoter. Immunohistochemistry analysis was conducted to measure the positive cell number of SPI1 and HK2 in melanoma tissues. The cell migration abilities were determined using a wound healing assay. Glucose consumption, pyruvate dehydrogenase activity, lactate production and ATP levels were measured to assess glycolysis. SPI1 transcription in melanoma cells and tissues was dramatically higher than that in adjacent normal tissues and epidermal melanocyte HEMa\u2010LP, respectively. Knockdown of SPI1 restrained cell viability, metastasis and glycolysis in melanoma cells. SPI1 directly targeted HK2, and knockdown of SPI1 repressed HK2 expression. Overexpression of HK2 weakened the inhibitory effects of SPI1 knockdown on the viability, metastasis and glycolysis of melanoma cells. The serine\u2013threonine kinase 1 (AKT1)\/mammalian target of rapamycin (mTOR) axis is involved in melanoma progression. SPI1 knockdown restrained melanoma cell proliferation, metastasis and glycolysis by regulating the AKT1\/mTOR pathway.<\/jats:p>","DOI":"10.1111\/jcmm.17844","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T08:40:37Z","timestamp":1691138437000},"page":"2675-2683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>SPI1<\/scp> involvement in malignant melanoma pathogenesis by regulation of <scp>HK2<\/scp> through the <scp>AKT1<\/scp>\/<scp>mTOR<\/scp> pathway"],"prefix":"10.1111","volume":"27","author":[{"given":"Chunlei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of dermatology Xiangyang No.1 People's Hospital, Hubei University of Medicine  Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of oncology Xiangyang No.1 People's Hospital, 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