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Lize Gu,1,* Qing Li,2,* Hao Liu,3,* Xun Lu,4 Mingchen Zhu5 1Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, People’s Republic of China; 2Department of Pathology, Shanghai Pudong New Area People’s Hospital, Shanghai 201299, People’s Republic of China; 3Department of Infection, Children’s Hospital of Nanjing Medical University, Nanjing 210004, People’s Republic of China; 4Milken School of Public Health, George Washington University, Washington, DC 20052, USA; 5Department of Clinical Laboratory, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingchen ZhuDepartment of Clinical Laboratory, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, People’s Republic of ChinaEmail sjnh_4914@163.comQing LiDepartment of Pathology, Shanghai Pudong New Area People’s Hospital, Shanghai 201299, People’s Republic of ChinaEmail green_liqing10@sina.comPurpose: Paclitaxel (PTX) is a first-line chemotherapeutic agent for treating ovarian cancer. However, PTX resistance has become a major obstacle in ovarian cancer therapy. The underlying mechanism associated with PTX resistance is still unclear.Patients and Methods: We used qPCR to detect taurine up-regulated 1 (TUG1) expression in normal ovarian tissues and ovarian tumor tissues. A combination of small interfering RNA (siRNA), cell counting kit 8 (CCK8), colony formation assay and nude mouse model were used to detect the effect of TUG1 on ovarian cancer cell PTX-resistance. Autophagy/cytotoxicity dual staining assay, luciferase reporter assay, Western blot and RNA-binding protein immunoprecipitation assay were used for further mechanistic studies.Results: TUG1 is highly expressed not only in ovarian tumor tissues compared with normal ovarian tissues but also in the chemo-resistant group compared with the sensitive group. Knockdown of TUG1 by siRNA decreased ovarian cancer cell and xenograft tumor PTX resistance with or without PTX treatment. Moreover, deletion of TUG1 in ovarian cancer cells decreased autophagosome formation and increased apoptosis as demonstrated by autophagy/cytotoxicity dual staining and Western blot assays. Furthermore, microRNA-29b-3p (miR-29b-3p) was found as the direct target of TUG1. Additionally, TUG1 could directly bind Ago2, a key protein of the RNA-induced silencing complex.Conclusion: Our findings suggest that TUG1, through targeting miR-29b-3p, induces autophagy and consequently results in PTX resistance in ovarian cancer.Keywords: ovarian cancer, lncRNA, TUG1, autophagy, sponge, miR-29b-3p

The rules issued by third-party applications may have direct violations or indirect violations with existing security flow rules in the SDN (software-defined network), thereby leading to the failure of security rules. Currently, existing methods cannot detect the rule collision in a comprehensive and fine-grained manner. This paper proposes a deep detection mechanism for rule collision that can detect grammatical errors in the flow rules themselves, and can also detect direct and indirect rule collisions between third-party and security applications based on the set intersection method. In addition, our mechanism can effectively and automatically resolve the rule collision. Finally, we implement the detection mechanism in the RYU controller, and use Mininet to evaluate the function and performance. The results show that the mechanism proposed in this paper can accurately detect the static, dynamic and dependency collisions of flow rules, and ensure that the decline of throughput of the northbound interface of the SDN network is controlled at 20%.