KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma

Fu, Xiaowei; Zhu, Yaqiong; Zheng, Bingbing; Zou, Yeqing; Wang, Chao; Wu, Peng; Wang, Jun; Chen, Haimin; Du, Pengcheng; Liang, Bo; Lü, Fang

doi:10.3892/ijo.2018.4348

Cited by 42 publications

(63 citation statements)

References 37 publications

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“…Several studies have shown that KIFC1 is associated with an apoptosis pathway [24,25]. We used RNA interference targeting KIFC1 in DU145-DR and C4-2-DR cells and confirmed the efficiency of KIFC1 knockdown by Western blotting ( Figure 3A).…”

Section: Inhibition Of Kifc1 Induces Apoptosis Pathway and Reverses Dsupporting

confidence: 60%

KIFC1 inhibitor CW069 induces apoptosis and reverses resistance to docetaxel in prostate cancer

Sekino¹,

Koike²,

Sakamoto³

et al. 2019

European Urology Supplements

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Kinesin family member C1 (KIFC1) is a minus end-directed motor protein that plays an essential role in centrosome clustering. Previously, we reported that KIFC1 is involved in cancer progression in prostate cancer (PCa). We designed this study to assess the involvement of KIFC1 in docetaxel (DTX) resistance in PCa and examined the effect of KIFC1 on DTX resistance. We also analyzed the possible role of a KIFC1 inhibitor (CW069) in PCa. We used DTX-resistant PCa cell lines in DU145 and C4-2 cells to analyze the effect of KIFC1 on DTX resistance in PCa. Western blotting showed that KIFC1 expression was higher in the DTX-resistant cell lines than in the parental cell lines. Downregulation of KIFC1 re-sensitized the DTX-resistant cell lines to DTX treatment. CW069 treatment suppressed cell viability in both parental and DTX-resistant cell lines. DTX alone had little effect on cell viability in the DTX-resistant cells. However, the combination of DTX and CW069 significantly reduced cell viability in the DTX-resistant cells, indicating that CW069 re-sensitized the DTX-resistant cell lines to DTX treatment. These results suggest that a combination of CW069 and DTX could be a potential strategy to overcome DTX resistance.

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Section: Inhibition Of Kifc1 Induces Apoptosis Pathway and Reverses Dsupporting

confidence: 60%

KIFC1 inhibitor CW069 induces apoptosis and reverses resistance to docetaxel in prostate cancer

Sekino¹,

Koike²,

Sakamoto³

et al. 2019

European Urology Supplements

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“…Various cancers also have increased Ran expression and enhanced RanGTP gradients due to increased DNA content (Hasegawa et al, 2013; Sheng et al, 2018; Xia et al, 2008). Some cancers also have increased HSET expression, which often correlates with metastasis and poor prognosis (Fu et al, 2018; Liu et al, 2016; Pannu et al, 2015; Patel et al, 2018). We propose that in cancer cells with increased HSET expression, the enhanced RanGTP gradients from higher DNA content promote HSET localization to the spindle, with a bias to the spindle poles that facilitates centrosome clustering by increased HSET-mediated cross-linking and sliding (Fig.…”

Section: Resultsmentioning

confidence: 99%

RanGTP induces an effector gradient of XCTK2 and importin α/β for spindle microtubule cross-linking

Ems-McClung

Emch

Zhang

et al. 2020

Journal of Cell Biology

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High RanGTP around chromatin is important for governing spindle assembly during meiosis and mitosis by releasing the inhibitory effects of importin α/β. Here we examine how the Ran gradient regulates Kinesin-14 function to control spindle organization. We show that Xenopus Kinesin-14, XCTK2, and importin α/β form an effector gradient that is highest at the poles and diminishes toward the chromatin, which is opposite the RanGTP gradient. Importin α and β preferentially inhibit XCTK2 antiparallel microtubule cross-linking and sliding by decreasing the microtubule affinity of the XCTK2 tail domain. This change in microtubule affinity enables RanGTP to target endogenous XCTK2 to the spindle. We propose that these combined actions of the Ran pathway are critical to promote Kinesin-14 parallel microtubule cross-linking to help focus spindle poles for efficient bipolar spindle assembly. Furthermore, our work illustrates that RanGTP regulation in the spindle is not simply a switch, but rather generates effector gradients where importins α and β gradually tune the activities of spindle assembly factors.

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“…KIFC1 is a minus end‐directed motor protein that is known for centrosome clustering in cancer cells . KIFC1 has been reported as a potential prognostic factor and therapeutic target in HCC, and a target protein of miR‐338‐3p in renal cell carcinoma . We then investigated expression of PKM2 and KIFC1 in HCC tissues and cell lines.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR‐338‐3p/PKM2 Axis Under Hypoxic Stress

et al. 2019

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Glucose metabolism reprogramming, which is a well‐established characteristic of multiple cancers, demands a higher rate of glycolysis to meet the increasing demands for macromolecular synthesis and to maintain rapid proliferation in a hypoxic environment. However, the mechanism underlying this switch remains to be elucidated. In this study, we investigated the function of circular RNA MAT2B (circMAT2B) in hepatocellular carcinoma (HCC) glucose metabolism reprogramming and malignancy. CircMAT2B was identified by bioinformatics analysis of Gene Expression Omnibus data sets. CircMAT2B expression was up‐regulated in HCC tissues and cell lines. HCC patients with high circMAT2B expression had shortened overall survival. We analyzed the positive correlation between glycolysis and circMAT2B expression in HCC using a maximum standardized uptake value determined by preoperative positron emission tomography/computed tomography scanning combined with high‐performance liquid chromatography assessment of the metabolites of glycolysis and the citric acid cycle. The effect of circMAT2B on glycolysis was validated in vitro and in vivo under hypoxic (1% O2) conditions. Functional assays were performed in HCC cells, HCC organoids, and nude mice to explore the tumor‐promoting roles of circMAT2B in HCC. Biotin‐coupled probe pull‐down assays, biotin‐coupled microRNA capture, luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation assays were performed to confirm the interaction among different RNAs. Mechanistically, we demonstrated that circMAT2B up‐regulated expression levels of the microRNA (miR)‐338‐3p target gene PKM2, which encodes a key enzyme in the process of glycolysis, through “sponging” miR‐338‐3p; thus, glycolysis and HCC progression are promoted through this mechanism. Conclusion: CircMAT2B promoted HCC progression by enhanced glycolysis by activating the circMAT2B/miR‐338‐3p/PKM2 axis under hypoxia, which may provide a therapeutic target for HCC.

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KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma

Cited by 42 publications

References 37 publications

KIFC1 inhibitor CW069 induces apoptosis and reverses resistance to docetaxel in prostate cancer

KIFC1 inhibitor CW069 induces apoptosis and reverses resistance to docetaxel in prostate cancer

RanGTP induces an effector gradient of XCTK2 and importin α/β for spindle microtubule cross-linking

Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR‐338‐3p/PKM2 Axis Under Hypoxic Stress

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