Department of Dermatology, Longgang Central Hospital, Shenzhen, China.
Department of Dermatology, Longgang Central Hospital, Shenzhen, China.
Acta Histochem. 2024 Oct;126(5-7):152186. doi: 10.1016/j.acthis.2024.152186. Epub 2024 Aug 13.
Cutaneous melanoma (cM) is a prevalent invasive cancer resulting from the malignant transformation of melanocytes. At present, the primary treatment for melanoma is surgical resection, which is not appropriate for patients with metastasis. Therefore, it is necessary to identify effective therapeutic targets for the early diagnosis and treatment of metastatic melanoma. Acyl-CoA thioesterase 7 (ACOT7) has been reported to be involved in the progression of multiple cancer, while its role in melanoma has not been extensively researched. Through gain-of-function and loss-of-function experiments, ACOT7 was identified as a tumor promoter that facilitates the progression of melanoma cells. Cell proliferation was promoted by overexpressing ACOT7 in M14 cells, and was suppressed by silencing ACOT7 in MeWo cells. Knockdown of ACOT7 induced cell cycle arrest by increasing the expressions of cyclin dependent kinase inhibitor 1B (P27) and cyclin dependent kinase inhibitor 1 A (P21), while simultaneously reducing proliferating cell nuclear antigen (PCNA) expression. Upregulation of ACOT7 promoted the cell cycle of melanoma cells. Additionally, apoptosis was induced by the absence of ACOT7 through activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The metastatic and invasive capacity of melanoma cells was significantly enhanced by the overexpression of ACOT7 and inhibited by the downregulation of ACOT7. Moreover, the cAMP responsive element binding protein 1 (CREB1) positively regulates ACOT7 expression by binding to its promoter region. A decrease of cell proliferation, migration and invasion, as well as an increase of cell apoptosis induced by silencing CREB1 were obviously reversed by ACOT7. In summary, ACOT7 transcriptionally activated by CREB1 elevates the progression of cM.
皮肤黑色素瘤（cM）是一种常见的侵袭性癌症，源于黑色素细胞的恶性转化。目前，黑色素瘤的主要治疗方法是手术切除，但对于转移患者并不适用。因此，有必要确定有效的治疗靶点，以便对转移性黑色素瘤进行早期诊断和治疗。酰基辅酶 A 硫酯酶 7（ACOT7）已被报道参与多种癌症的进展，但其在黑色素瘤中的作用尚未得到广泛研究。通过功能获得和功能丧失实验，发现 ACOT7 是一种促进肿瘤的物质，可促进黑色素瘤细胞的进展。在 M14 细胞中过表达 ACOT7 可促进细胞增殖，而在 MeWo 细胞中沉默 ACOT7 则抑制细胞增殖。ACOT7 的敲低通过增加细胞周期蛋白依赖性激酶抑制剂 1B（P27）和细胞周期蛋白依赖性激酶抑制剂 1A（P21）的表达，同时降低增殖细胞核抗原（PCNA）的表达，诱导细胞周期停滞。ACOT7 的上调促进了黑色素瘤细胞的细胞周期。此外，通过激活半胱天冬酶-3 和多聚（ADP-核糖）聚合酶（PARP），ACOT7 的缺失可诱导细胞凋亡。ACOT7 的过表达显著增强了黑色素瘤细胞的转移和侵袭能力，而 ACOT7 的下调则抑制了其转移和侵袭能力。此外，cAMP 反应元件结合蛋白 1（CREB1）通过结合其启动子区域，正向调节 ACOT7 的表达。沉默 CREB1 引起的细胞增殖、迁移和侵袭减少以及细胞凋亡增加，可被 ACOT7 明显逆转。综上所述，CREB1 转录激活的 ACOT7 可促进 cM 的进展。
