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.
Melanoma is the most aggressive type of skin cancer with a rapid progression and a limited efficiency of therapeutics. Recently, studies have identified some microRNAs playing important roles in the development of melanoma. Syndecan-1 (Syn-1), dysregulated in many cancers, plays important roles in tumor progression by controlling cell proliferation. In this study, we investigated whether microRNA-143 (miR-143) is involved in the regulation of Syn-1 and thus plays a functional role in melanoma. We found that miR-143 expression was significantly lower in melanoma tissues than in normal tissues and its low expression was closely related to clinical stages of melanoma. Further experiments showed that consistent with the inhibitory effects induced by knockdown of Syn-1, overexpression of miR-143 suppressed cell proliferation, promoted G1 phase arrest and induced apoptosis in melanoma. Downregulation of miR-143 apparently produced opposite effects. Combined treatment of miR-143 overexpression and Syn-1 knockdown induced remarkable synergistic effects, while reconstitution of miR-143-resistant Syn-1 reversed the inhibitory activity of miR-143. Moreover, miR-143 level was inversely correlated with Syn-1 expression in melanoma cells. miR-143 directly targeted the 3′-untranslated regions of Syn-1 mRNA and they were in the same Argonaute2 complex. Taken together, this study revealed a link between miRNA-143 and Syn-1 in the pathogenesis of melanoma. MiR-143 plays an important role in the regulation of cell growth in melanoma. Restoration of miR-143 expression may represent a promising and efficient therapeutic approach for targeting malignant melanoma.
Disassembly is a core procedure in remanufacturing. Disassembly is currently carried out mainly by human operators. It is important to reduce the labor content of dis-assembly through automation, to make remanufacturing more economically attractive. Threaded fastener removal is one of the most difficult disassembly tasks to be fully automated. This article presents a new method developed for automating the unfastening of screws. An electric nutrunner spindle with a geared offset adapter was fitted to the end of a collaborative robot. The position of a hexagonal headed screw in a fitted stage was known only approximately, and its orientation in the hole was unknown. The robot was programed to perform a spiral search motion to engage the tool onto the screw. A control strategy combining torque and position monitoring with active compliance was implemented. An existing robot cell was modified and utilized to demonstrate the concept and to assess the feasibility of the solution using a turbocharger as a disassembly case study. Note to Practitioners-Remanufacturing is known to generate substantial economic, social, and environmental benefits. Disassembly is the first operation in a remanufacturing process chain. Unfastening threaded parts ("unscrewing") is a common disassembly task accounting for approximately 40% of all disassembly activity. Like other disassembly tasks, often, unscrewing has to be carried out manually in remanufacturing due to difficulties caused by the variable and unpredictable condition of the end-of-life (EoL) products to be remanufactured. Automating unscrewing operations should reduce the labor content of disassembly, thus lowering remanufacturing costs and promoting the adoption of remanufacturing. This article proposes the use
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