Melanoma is the major lethal skin malignancy.However, the critical molecular drivers governing melanoma progression and prognosis are still not clear.By analyzing The Cancer Genome Atlas (TCGA) data, we identified FUT8-AS1 as a prognosis-related long non-coding RNA (lncRNA) in melanoma.We further confirmed that FUT8-AS1 is downregulated in melanoma.Reduced expression of FUT8-AS1 is correlated with aggressive clinical factors and inferior overall survival.
Using in vitro functional assays, our findings demonstrated that ectopic expression of FUT8-AS1 represses melanoma cell proliferation, migration, and invasion.FUT8-AS1 Pet Booster Seat silencing promotes melanoma cell proliferation, migration, and invasion.Furthermore, in vivo functional assays demonstrated that FUT8-AS1 represses melanoma growth and metastasis.Mechanistically, FUT8-AS1 was found to bind NF90, repress the interaction between NF90 and primary miR-145 (pri-miR-145), relieve the repressive roles of NF90 on mature miR-145-5p biogenesis, and thus promote miR-145-5p biogenesis and upregulate mature miR-145-5p level.The expression of FUT8-AS1 is positively correlated with miR-145-5p in melanoma tissues.
Via upregulating miR-145-5p, FUT8-AS1 reduces the expression of NRAS, a target of miR-145-5.FUT8-AS1 further represses MAPK signaling via downregulating NRAS.Functional rescue assays demonstrated that inhibition of miR-145-5p reverses the tumor suppressive roles of FUT8-AS1 in melanoma.The oncogenic roles of FUT8-AS1 silencing are also blocked by MAPK signaling inhibitor MEK162.In conclusion, these findings demonstrate that FUT8-AS1 exerts tumor suppressive roles in melanoma via regulating NF90/miR-145-5p/NRAS/MAPK signaling axis.
Targeting FUT8-AS1 and its downstream BCAA XDM SPIKED POWDER BERRIES molecular signaling axis represent promising therapeutic strategies for melanoma.