Targeted disruption of Nemo‐like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma

Jung, Kwang Hwa; Kim, Jeong Kyu; Noh, Ji Heon; Eun, Jung Woo; Bae, Hyun Jin; Xie, Hong; Ahn, Young Min; Park, Won Sang; Lee, Jung Young; Nam, Suk Woo

doi:10.1002/jcb.22579

Cited by 54 publications

(56 citation statements)

References 29 publications

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“…It has been reported that NLK was significantly overexpressed in the HCC specimens compared to corresponding normal tissues in Korean patients [12]. In order to further confirm the results above and explore the physiological or pathological relationship between expression of NLK and proliferation index Ki-67 in HCC samples in Chinese patients, we first detected the levels of NLK and Ki-67 in a series of 136 HCC tissues by immunohistochemical staining.…”

Section: Resultsmentioning

confidence: 83%

“…Furthermore, expression of NLK was also significantly upregulated in HCC specimens compared to corresponding normal tissues in Korean patients, based on the Western blot analysis and RT-PCR of five selected HCCs and corresponding normal tissues and immunohistochemical analysis of TMA containing 30 HCCs and 20 normal tissues. Targeted disruption of NLK could inhibit the proliferation of Hep3B cells and arrest cell cycle transition [12].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma

Chen

Qiao

et al. 2015

Tumor Biol.

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Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine protein kinase and belongs to the extracellular signal-regulated kinases/microtubule-associated protein kinase families (Erks/MAPKs). Previous studies have indicated that abnormal expressions of NLK played critical roles in various types of human cancers. Recent studies suggested that NLK expression was significantly upregulated in the hepatocellular carcinoma (HCC) specimens. However, the clinical significance of NLK expression in HCC remains largely unknown. In this study, we focused on the clinical significance of NLK in HCC and found that high expression of NLK was significantly associated with Edmondson-Steiner grade (P = 0.002), tumor size (P = 0.022), and no. of tumor nodules (P < 0.001), and NLK was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that NLK expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that NLK expression was an independent prognostic indicator for HCC (P = 0.0370). In conclusion, NLK overexpression is associated with poor overall survival in patients with HCC, it might be an independent poor prognostic marker for HCC.

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Section: Resultsmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma

Chen

Qiao

et al. 2015

Tumor Biol.

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“…Targeted deletion of NLK can suppress the growth of hepatocellular carcinoma through inhibition of CDK2 and Cyclin D1, suggesting that NLK may play a role in promoting the growth of hepatoma cells by promoting cell cycle progression (Jung et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nemo-like Kinase Increases Taxol Sensitivity in Laryngeal Cancer

Dong

Guo²,

Zhao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…NLK is an evolutionary conservative kinase and exerts its diverse function in embryonic patterning, nervous system development, and human cancers due to its capacity to regulate signaling, including Wnt/b-catenin, Notch, IL6, and activin (36,(40)(41)(42). NLK is known to phosphorylate LEF1, a key transcription factor in the Wnt signaling pathway at Thr155 and Ser166 residues (34).…”

Section: Discussionmentioning

confidence: 99%

microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma

Tan

Mou

et al. 2017

Clinical Cancer Research

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Purpose: MYCN is one of the most well-characterized genetic markers of neuroblastoma. However, the mechanisms as to how MYCN mediate neuroblastoma tumorigenesis are not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated neuroblastoma tumorigenesis, supporting their potential as therapeutic targets for neuroblastoma. Although miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated neuroblastoma progression remains largely elusive.Experimental Design: The expression of miR-221 in the formalin-fixed, paraffin-embedded tissues from 31 confirmed patients with neuroblastoma was detected by locked nucleic acid-in situ hybridization and qRT-PCR. The correlation between miR-221 expression and clinical features in patients with neuroblastoma was assessed. The mechanisms as to how miR-221 regulate MYCN in neuroblastoma were addressed. The effect of miR-221 on cellular proliferation in neuroblastoma was determined both in vitro and in vivo.Results: miR-221 was significantly upregulated in neuroblastoma tumor cells and tissues that overexpress MYCN, and high expression of miR-221 was positively associated with poor survival in patients with neuroblastoma. Nemo-like kinase (NLK) as a direct target of miR-221 in neuroblastoma was verified. In addition, overexpression of miR-221 decreased LEF1 phosphorylation but increased the expression of MYCN via targeting of NLK and further regulated cell cycle, particularly in S-phase, promoting the growth of neuroblastoma cells.Conclusions: This study provides a novel insight for miR-221 in the control of neuroblastoma cell proliferation and tumorigenesis, suggesting potentials of miR-221 as a prognosis marker and therapeutic target for patients with MYCN overexpressing neuroblastoma.

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Targeted disruption of Nemo‐like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma

Cited by 54 publications

References 29 publications

Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma

Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma

Inhibition of Nemo-like Kinase Increases Taxol Sensitivity in Laryngeal Cancer

microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma

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