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      KIF2C promotes the proliferation of hepatocellular carcinoma cells in vitro and in vivo

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          Abstract

          Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality and morbidity rates. In recent years, HCC targeted therapy has gained increasing attention. Due to the heterogeneity and high metastasis of HCC, more effective therapeutic targets are needed. Kinesin family member 2C (KIF2C), also known as mitotic centromere-associated kinesin, is a microtubule-based motor protein which is involved in a variety of important cellular processes, such as mitosis. The effects of KIF2C on cancer progression and development have been widely studied; however, its potential effects on HCC remains unclear. In the present study, high expression of KIF2C in human HCC tissues was demonstrated using The Cancer Genome Atlas database and immunohistochemistry assays. KIF2C expression was associated with HCC prognosis, including overall survival and disease-free survival. KIF2C expression was also associated with clinical pathological characteristics including the number of tumor nodes (P=0.015) and tumor size (P=0.009). KIF2C knockdown inhibited the proliferation of HCC cells in vitro, confirmed by MTT and colony formation assays, and suppressed tumor growth in mice which was confirmed by a xenograft mouse model. Together, the results suggested that KIF2C may serve as a promising therapeutic target for the treatment of HCC.

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          Most cited references36

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            Kinesins and cancer.

            Kinesins are a family of molecular motors that travel unidirectionally along microtubule tracks to fulfil their many roles in intracellular transport or cell division. Over the past few years kinesins that are involved in mitosis have emerged as potential targets for cancer drug development. Several compounds that inhibit two mitotic kinesins (EG5 (also known as KIF11) and centromere-associated protein E (CENPE)) have entered Phase I and II clinical trials either as monotherapies or in combination with other drugs. Additional mitotic kinesins are currently being validated as drug targets, raising the possibility that the range of kinesin-based drug targets may expand in the future.
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              Genome stability is ensured by temporal control of kinetochore-microtubule dynamics

              Summary Most solid tumors are aneuploid and many frequently mis-segregate chromosomes. This chromosomal instability is commonly caused by persistent maloriented attachment of chromosomes to spindle microtubules. Chromosome segregation requires stable microtubule attachment at kinetochores, yet those attachments must be sufficiently dynamic to permit correction of malorientations. How this balance is achieved is unknown, and the permissible boundaries of attachment stability versus dynamics essential for genome stability remain poorly understood. Here we show that two microtubule-depolymerizing kinesins, Kif2b and MCAK, stimulate kinetochore-microtubule dynamics during distinct phases of mitosis to correct malorientations. Few-fold reductions in kinetochore-microtubule turnover, particularly in early mitosis, induce severe chromosome segregation defects. In addition, we show that stimulation of microtubule dynamics at kinetochores restores chromosome stability to chromosomally unstable tumor cell lines, establishing a causal relationship between deregulation of kinetochore-microtubule dynamics and chromosomal instability. Thus, temporal control of microtubule attachment to chromosomes during mitosis is central to genome stability in human cells.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                October 2021
                02 August 2021
                02 August 2021
                : 22
                : 4
                : 1094
                Affiliations
                [1 ]Department of Clinical Medicine, School of Medicine, Xuchang University, Xuchang, Henan 461000, P.R. China
                [2 ]Department of General Surgery, The Secondary Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
                Author notes
                Correspondence to: Professor Zhenya Gao, Department of Clinical Medicine, School of Medicine, Xuchang University, 1389 Xufan Road, Xuchang, Henan 461000, P.R. China zhygao1221@ 123456126.com
                Article
                ETM-0-0-10528
                10.3892/etm.2021.10528
                8383772
                34504548
                e6070ab6-a2da-4f54-8c55-2c2a1a82afdd
                Copyright: © Gao et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 07 March 2020
                : 26 August 2020
                Funding
                Funding: No funding was received.
                Categories
                Articles

                Medicine
                hepatocellular carcinoma,kinesin family member 2c,proliferation,clinical pathological features,therapeutic target

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