Chondrosarcomas are malignant cartilage-forming tumors of bone which exhibit resistance to both chemotherapy and radiation treatment. miRNAs have been well demonstrated to regulate gene expression and play essential roles in a variety of biological processes, including proliferation, differentiation, migration, cell cycling and apoptosis. In this study, we obtained evidence that miR-100 acts as a tumor suppressor in human chondrosarcomas. Interestingly, cisplatin resistant chondrosarcoma cells exhibit decreased expression of miR-100 compared with parental cells. In addition, we identified mTOR as a direct target of miR-100. Overexpression of miR-100 complementary pairs to the 3' untranslated region (UTR) of mTOR, resulted in sensitization of cisplatin resistant cells to cisplatin. Moreover, recovery of the mTOR pathway by overexpression of S6K desensitized the chondrosarcoma cells to cisplatin, suggesting the miR-100-mediated sensitization to cisplatin dependent on inhibition of mTOR. In summary, the present studies highlight miR-100 as a tumor suppressor in chondrosarcoma contributing to anti-chemoresistance. Overexpression of miR-100 might be exploited as a therapeutic strategy along with cisplatin-based combined chemotherapy for the treatment of clinical chondrosarcoma patients.

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> Osteosarcoma is the most common malignant bone tumor with high incidence in adolescence and poor prognosis. RBM10, a member of RBPs, was reported to be a tumor suppressor in many kinds of cancers. However, the roles of RBM10 in osteosarcoma remain unknown. In this study, we found that overexpression of RBM10 decreased osteosarcoma cell proliferation and colony formation in soft agar, and inhibited osteosarcoma cell migration and invasion. Our results also revealed that RBM10 overexpression induced osteosarcoma cell apoptosis via the inhibition of Bcl-2, the activation of caspase-3, and the transcription and production of TNF-α. Our results indicated that RBM10 acts as a tumor suppressor in osteosarcoma. This could enable to define a new strategy for diagnosis and treatment of patients with osteosarcoma. lian cells [15]. However, RBM10 is mutated in a number of cells, which is associated with many diseases, including neurological, muscular, sensory or cancers [15][16][17][18][19][20][21][22]. In recent years, it was reported that RBM10 was a tumor suppressor in many types of cancers, such as lung cancer and breast cancer [23]. Of note, overexpression of RBM10 increases apoptosis via elevated level of TNF-α mRNA and soluble TNF-α protein [24]. LUAD-associated RBM10 mutations, which exhibit a mutational spectrum similar to that of tumor suppressor genes, have been associated to a decrease in cell proliferation [25]. RBM10 also decreases colony formation and xenograft tumor growth in lung cancer [8,12]. However, the role of RBM10 in cancer progression is controversial. Loiselle et al. reported that RBM10 expression contributes to tumor growth and metastasis in RBM5-null tumors [26], suggesting that it can also act as a tumor promoter. Surprisingly, there is no studies on the roles and mechanisms of RBM10 in osteosarcoma. In this study, we report that overexpression of RBM10 significantly decreases osteosarcoma cell growth, including cell proliferation and colony formation in soft agar, and inhibits osteosarcoma cell migration and invasion. Our results also revealed that RBM10 overexpression induces osteosarcoma cell apoptosis via the inhibition of Bcl-2, the activation of caspase-3, and the production of TNF-α. These results suggest that RBM10 acts as a tumor suppressor in osteosarcoma. and it might be a novel biomarker for diagnosis and represent a new avenue for the treatment of patients with osteosarcoma.

Abstract:Voltage source converter (VSC)-based high voltage direct current (VSC-HVDC) interconnectors can realize accurate and fast control of power transmission among AC networks, and provide emergency power support for AC networks. VSC-HVDC interconnectors bring exclusive fault characteristics to AC networks, thus influencing the performance of traditional protections. Since fault characteristics are related to the control schemes of interconnectors, a fault ride-through (FRT) strategy which is applicable to the interconnector operating characteristic of working in four quadrants and capable of eliminating negative-sequence currents under unbalanced fault conditions is proposed first. Then, the additional terms of measured impedances of distance relays caused by fault resistances are derived using a symmetrical component method. Theoretical analysis shows the output currents of interconnectors are controllable after faults, which may cause malfunctions in distance protections installed on lines emanating from interconnectors under the effect of fault resistances. Pilot protection is also inapplicable to lines emanating from interconnectors. Furthermore, a novel pilot protection principle based on the ratio between phase currents and the ratio between negative-sequence currents flowing through both sides is proposed for lines emanating from the interconnectors whose control scheme aims at eliminating negative-sequence currents. The validity of theoretical analysis and the protection principle is verified by PSCAD/EMTDC simulations.

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