Study On The Mechanisms Of MiR-489-3p/SIX1 Axis In Regulation Of Growth And Metastasis In Melanoma

Melanoma is the most aggressive and lethal form of skin cancers.It is characterized as a cancer of early metastasis and high recurrence rate.The incidence of melanoma has increased rapidly in recent years.Due to its poor sensitivity to both chemotherapy and radiation therapy,it is crucial to explore pathogenesis for melanoma prevention,treatment,and prognosis.The onset of melanoma 1s a multi-factorial,multi-gene regulation process.The SIX1 gene is a highly conserved transcription factor which belongs to homeobox gene family.It plays an important role in the development of many tissues and organs.Recently,SIX1 has been shown to be a key factor regulating tumor aerobic glycolysis in tumors.,which means it has a significant role to play in cancer and tumorigenesis.However,the clinical significance and functions of SIX1 in melanoma are unknown.MicroRNAs are a class of single-stranded non-coding RNAs consisting of 19-22 nucleotides,which play an important role in the regulation of tumors.Both up-regulation and down-regulation of tumors have been reported to be associated with tumourigenesis.A variety of microRNAs have been shown to be involved in the regulation of some important signaling pathways in melanoma regulation,microRNAs are potential therapeutic targets for melanoma.miR-489-3p has been shown to have a tumor suppressive effect in a variety of tumors,but regulation of miR-489-3p in melanoma has not been reported.Our study demonstrates that in melanoma,miR-489-3p is an upstream negative regulator of SIX1 and inhibits SIX1 expression by targeted binding to the 3’-UTR region of SIX1.The miR-489-3p/SIX1 axis can effectively regulate the proliferation,migration,invasion and aerobic glycolysis of melanoma cells,and in vivo animal experiments have also confirmed the conclusion.Through clinical analysis,it is found that in the tumor tissues of melanoma patients,the expression of miR-489-3p is down-regulated,while the expression of SIX1 is up-regulated,the expressions of which are negatively correlated.In conclusion,we demonstrate that miR-489-3p/SIX1 axis is effective in the regulation of aerobic glycolysis in melanoma,which may provide a new strategy for the treatment of melanoma.