LncRNA FOXC2-AS1 stimulates proliferation of melanoma via silencing p15 by recruiting EZH2

D.-F. Xu, X.-H. Tao, Y. Yu, Y. Teng, Y.-M. Huang, J.-W. Ma, Y.-B. Fan

Department of Dermatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China. 3100102508@zju.edu.cn

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• Oncology

OBJECTIVE: The aim of this study was to elucidate the role of FOXC2-AS1 in promoting the proliferative ability and inhibiting apoptosis of melanoma by silencing p15, thereafter regulating the progression of melanoma.

PATIENTS AND METHODS: FOXC2-AS1 levels in melanoma patients with or without metastasis and those with the tumor in different stages were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Regulatory effects of FOXC2-AS1 on viability and apoptosis in melanoma cells were assessed, and subcellular distribution of FOXC2-AS1 was analyzed. Subsequently, the interactions of FOXC2-AS1 with EZH2 and SUZ12 were explored by RNA-Binding Protein Immunoprecipitation (RNA-RIP) assay. Through chromatin immunoprecipitation (ChIP) assay, the role of FOXC2-AS1 to regulate p15 transcription by recruiting EZH2 was verified. At last, regulatory effects of FOXC2-AS1/p15 axis on viability and apoptosis in melanoma cells were investigated.

RESULTS: It was found that FOXC2-AS1 was upregulated in melanoma tissues, especially those with metastasis or stage II-IV. Melanoma patients expressing high level of FOXC2-AS1 showed worse survival than those with low level. Knockdown of FOXC2-AS1 inhibited viability, and stimulated apoptosis in A375 and sk-mel-110 cells. Besides, P15 level was upregulated in melanoma cells transfected with si-FOXC2-AS1, and FOXC2-AS1 was mainly distributed in cytoplasm. RNA-RIP assay confirmed that FOXC2-AS1 was mainly enriched in anti-EZH2 and aniti-SUZ12. Knockdown of EZH2 could markedly upregulate protein level of p15 in melanoma cells. Furthermore, it was verified that FOXC2-AS1 inhibited p15 transcription via recruiting EZH2, and the knockdown of p15 could partially reverse the regulatory effects of FOXC2-AS1 on viability and apoptosis in melanoma.

CONCLUSIONS: FOXC2-AS1 stimulates proliferative ability in melanoma via silencing p15.

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