Li Ruiya, Zhang Lingli, Jia Lizhou, Duan Yan, Li Yan, Bao Lidao, Sha Na
Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
Department of Pathology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
PLoS One. 2014 Jun 26;9(6):e100893. doi: 10.1371/journal.pone.0100893. eCollection 2014.
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.
长链非编码RNA（lncRNAs）已被证明参与包括恶性黑色素瘤在内的癌症复杂网络，并在肿瘤发生和发展中发挥重要作用。然而，它们的功能和下游机制在很大程度上尚不清楚。本研究旨在探讨BRAF激活的非编码RNA（BANCR）这种新型的潜在黑色素瘤细胞调节因子是否参与恶性黑色素瘤的增殖，并阐明这一过程中的潜在机制。我们发现，BANCR在人恶性黑色素瘤细胞系和组织中异常高表达，并通过定量PCR检测发现其表达随肿瘤分期增加。shRNA转染诱导的BANCR敲低显著抑制肿瘤细胞增殖并使MAPK通路失活，尤其是通过沉默ERK1/2和JNK成分。此外，BANCR敲低与抑制ERK1/2或JNK（分别由特异性抑制剂U0126或SP600125诱导）的联合处理在体外产生协同抑制作用。并且ERK1/2或JNK诱导的抑制作用可通过BANCR过表达得到挽救。通过在BALB/c裸鼠中的致瘤性试验，我们进一步发现BANCR敲低在体内抑制肿瘤生长。此外，BANCR高表达的患者生存率较低。综上所述，我们证实了一种新型lncRNA BANCR在人恶性黑色素瘤中异常上调。BANCR在体外和体内均参与黑色素瘤细胞增殖。BANCR与MAPK通路之间的联系可能为恶性黑色素瘤增殖调控机制提供新的解释。
