Long non-coding RNAs (lncRNAs) have been shown to be implicated in the complex network of cancer including malignant melanoma and play important roles in tumorigenesis and progression.,However, their functions and downstream mechanisms are largely unknown.,This study aimed to investigate whether BRAF-activated non-coding RNA (BANCR), a novel and potential regulator of melanoma cell, participates in the proliferation of malignant melanoma and elucidate the underlying mechanism in this process.,We found that BANCR was abnormally overexpressed in human malignant melanoma cell lines and tissues, and increased with tumor stages by quantitative PCR.,BANCR knockdown induced by shRNA transfection significantly inhibited proliferation of tumor cells and inactivated MAPK pathway, especially by silencing the ERK1/2 and JNK component.,Moreover, combination treatment of BANCR knockdown and suppression ERK1/2 or JNK (induced by specific inhibitors U0126 or SP600125 respectively) produced synergistic inhibitory effects in vitro.,And the inhibitory effects induced by ERK1/2 or JNK could be rescued by BANCR overexpression.,By tumorigenicity assay in BALB/c nude mice, we further found that BANCR knockdown inhibited tumor growth in vivo.,In addition, patients with high expression of BANCR had a lower survival rate.,Taken together, we confirmed the abnormal upregulation of a novel lncRNA, BANCR, in human malignant melanoma.,BANCR was involved in melanoma cell proliferation both in vitro and in vivo.,The linkage between BANCR and MAPK pathway may provide a novel interpretation for the mechanism of proliferation regulation in malignant melanoma.
Mucosal melanomas in the head and neck region are most frequently located in the nasal cavity and paranasal sinuses.,Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas.,The aim was to determine the KIT, NRAS and BRAF mutation frequencies in a large series of primary SNMMs.,Laser capture microdissection was used to isolate tumour cells from 56 formalin-fixed paraffin-embedded tumours.,The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing.,Overall, 21% (12 out of 56) of SNMMs harboured KIT, NRAS or BRAF mutations.,Mutations in these oncogenes occurred in a mutually exclusive manner.,Both KIT and BRAF mutations were identified at a similar frequency of 4% each (2 out of 56), whereas NRAS mutations were detected in 14% (8 out of 56) of the SNMMs.,Four of the NRAS mutations were located in exon 1.,Mutations in these oncogenes were significantly more common in melanomas located in the paranasal sinuses than in nasal cavity (P=0.045).,In a multivariate analysis, patients with melanomas in the nasal cavity had a significantly better overall survival than those with tumours in the paranasal sinuses (P=0.027).,Our findings show that KIT and BRAF mutations, which are accessible for present targeted therapies, are only rarely present in SNMMs, whereas NRAS mutations seem to be relatively more frequent.,The data show that majority of SNMMs harbour alterations in genes other than KIT, NRAS and BRAF.