Department of Gastroenterology, Shangrao People's Hospital, Shangrao, 334000, Jiangxi Province, China.
Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
Sci Rep. 2023 Jun 5;13(1):9073. doi: 10.1038/s41598-023-36404-w.
Gene fusions caused by cytogenetic aberrations play important roles in the initiation and progression of cancers. The recurrent MTAP-ANRIL fusion gene was reported to have a frequency of greater than 7% in melanoma in our previous study. However, its functions remain unclear. Truncated MTAP proteins resulting from point mutations in the last three exons of MTAP can physically interact with the wild-type MTAP protein, a tumor suppressor in several human cancers. Similarly, MTAP-ANRIL, which is translated into a truncated MTAP protein, would influence wild-type MTAP to act as an oncogene. Here, we found that MTAP-ANRIL gene fusion downregulated the expression of wild-type MTAP and promoted epithelial-mesenchymal transition-like process through the activation of JNK and p38 MAPKs in vitro and in vivo. Our results suggest that MTAP-ANRIL is a potential molecular prognostic biomarker and therapeutic target for melanoma.
染色体异常引起的基因融合在癌症的发生和发展中起着重要作用。我们之前的研究报告称，在黑色素瘤中，反复出现的 MTAP-ANRIL 融合基因的频率大于 7%。然而，其功能仍不清楚。由于 MTAP 的最后三个外显子中的点突变而产生的截断的 MTAP 蛋白可以与野生型 MTAP 蛋白物理相互作用，野生型 MTAP 蛋白是几种人类癌症中的肿瘤抑制因子。同样，翻译成截断的 MTAP 蛋白的 MTAP-ANRIL 也会影响野生型 MTAP 作为癌基因发挥作用。在这里，我们发现 MTAP-ANRIL 基因融合通过在体外和体内激活 JNK 和 p38 MAPKs 下调野生型 MTAP 的表达，并促进上皮-间充质转化样过程。我们的研究结果表明，MTAP-ANRIL 是黑色素瘤潜在的分子预后生物标志物和治疗靶点。
