Abstract
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.
Highlights
Melanoma is the most aggressive type of skin cancer, characterized by a rapid progression, metastasis to regional lymph nodes and distant organs as well as a limited efficiency of therapeutics [1]
Growing attention has been given to a class of nonprotein-coding RNAs, known as long non-coding RNAs, which participates in cell fate determination and disease pathogenesis [5,6]
A significantly increased level of BRAF-activated non-coding RNA (BANCR) was seen in patients with malignant melanoma (Figure 1A, P = 0.007), compared with the levels detected in age/gender-matched controls with melanocytic nevus
Summary
Melanoma is the most aggressive type of skin cancer, characterized by a rapid progression, metastasis to regional lymph nodes and distant organs as well as a limited efficiency of therapeutics [1]. It accounts for only about 4% of all dermatological cancers, it contributes to more than 80% death of skin cancer patients [2]. HOTAIR seems to modulate tumor invasiveness by enhancing PRC2-mediated suppression of metastasis [8]. PRNCR1 and PCGEM1 can bind successively to androgen receptor and strongly enhance androgen receptor-mediated gene activation and proliferation in prostate cancer [9]. Dysregulation of HNF1A-AS1 participates in oesophageal tumorigenesis by modulation of chromatin and nucleosome assembly as well as by induction of cancer-related H19 [10]
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