Increased NEK2 in hepatocellular carcinoma promotes cancer progression and drug resistance by promoting PP1/Akt and Wnt activation

Wen, Sailan; Liu, Yuwu; Yang, Manyi; Yang, Keda; Huang, Jianghai; Feng, Daxiong

doi:10.3892/or.2016.5009

Cited by 28 publications

(22 citation statements)

References 31 publications

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“…Signaling by AKT, also known as protein kinase B, plays an important role in regulating cell survival and apoptosis[14]. Our results indicated that phosphorylation of AKT was up-regulated in Smoc2 overexpressed cells and down-regulated in Smoc2 siRNA interfered cells (Figure 6).…”

Section: Resultsmentioning

confidence: 64%

Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

Su¹,

Kuai²,

Li³

2016

WJG

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AIMTo determine the influence of Smoc2 on hepatocellular carcinoma (HCC) cell proliferation and to find a possible new therapeutic target for preventing HCC progression.METHODSWe detected expression of Smoc2 in HCC tissues and corresponding non-tumor liver (CNL) tissues using PCR, western blot, and immunohistochemistry methods. Subsequently, we down-regulated and up-regulated Smoc2 expression using siRNA and lentivirus transfection assay, respectively. Then, we identified the effect of Smoc2 on cell proliferation and cell cycle using CCK-8 and flow cytometry, respectively. The common cell growth signaling influenced by Smoc2 was detected by western blot assay.RESULTSThe expression of Smoc2 was significantly higher in HCC tissues compared with CNL tissues. Overexpression of Smoc2 promoted HCC cell proliferation and cell cycle progression. Down-regulation of Smoc2 led to inhibition of cell proliferation and cell cycle progression. Smoc2 had positive effect on ERK and AKT signaling.CONCLUSIONSmoc2 promotes the proliferation of HCC cells through accelerating cell cycle progression and might act as an anti-cancer therapeutic target in the future.

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Section: Resultsmentioning

confidence: 64%

Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

Su¹,

Kuai²,

Li³

2016

WJG

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“…Emerging evidence has documented that NEK2 is an important carcinoma biomarker for prognosis and serves as a therapeutic target . A recent report showed that NEK2 ectopic expression not only promotes hepatocellular cancer progression, but also activates drug resistance independent of protein phosphatase‐1/protein kinase B and Wnt/β‐catenin pathway activation . Zhou et al .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐128 promotes apoptosis in lung cancer by directly targeting NIMA‐related kinase 2

et al. 2017

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BackgroundMicroRNA‐128 (miR‐128) serves as a regulator by inducing cancer cell apoptosis, differentiation, the epithelial‐to‐mesenchymal transition process, and tumor growth by mediating different targets. NIMA‐related kinase 2 (NEK2) is aberrantly expressed in lung cancer. The miR‐128/NEK2 pathway has been reported to predict prognosis in colorectal cancer; however, the determination of a relationship between miR‐128 and NEK2 in lung cancer has remained elusive. We explored the association between miR‐128 and NEK2 in lung cancer.MethodsMiR‐128 and NEK2 expression were examined in 15 lung cancer tissues by real time‐PCR. Lung cancer SK‐MES‐1 cells were transfected with miR‐128 mimic, an inhibitor or a negative control. MiR‐128 and NEK2 expression levels were detected using quantitative real time‐PCR and Western blot. SK‐MES‐1 cell apoptosis was performed by flow cytometry.ResultsCompared to adjacent non‐tumor tissues, miR‐128 was downregulated and NEK2 was upregulated in 15 lung cancer tissues. Lung cancer SK‐MES‐1 cells transfected with miR‐128 mimic induced a higher apoptotic rate than those transfected with the negative control. Dual luciferase assay further confirmed that NEK2 was a direct target of miR‐128 in lung cancer, and transfection with miR‐128 mimic could decrease the NEK2 protein level while the miR‐128 inhibitor increased NEK2 expression. Finally, the apoptotic effect of lung cancer cells induced by miR‐128 mimic could be reversed by NEK2 overexpression.Conclusions NEK2 was regulated by miR‐128 in lung cancer and miR‐128 induced lung cancer cell apoptosis by mediating NEK2 expression.

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“…Some studies have suggested that NEK2 is overexpressed in HCC tissues compared with adjacent normal tissues and is associated with poor survival [24][25][26][27][28][29][30][31]. In addition, there is evidence showing that elevated NEK2 expression could enhance stem-like properties, drug resistance, and the progression of HCC [27,28]. However, a study by Fu et al reported that HCC patients with high NEK2 expression had better survival [32].…”

Section: Introductionmentioning

confidence: 91%

“…In addition to our cohort study, 9 of the previous studies were conducted in China [25,32,[39][40][41][42][43][44][45], and 1 in Japan [30]. The case numbers in each study ranged between [30,32,39,42,45], and 5 referring to liver cirrhosis [32,41,42,44,45]. The NOS scores of the studies included ranged from 5 to 7, indicating that the quality of these studies was moderate to high.…”

Section: Study Search and Study Characteristics In Meta-analysismentioning

confidence: 99%

The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study

Cheng

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Numerous studies have shown that NIMA-related kinase 2 (NEK2) expression in hepatocellular carcinoma (HCC) tissue is associated with survival and clinicopathological features; however, the evidence remains inconclusive. Thus, we aimed to further explore the prognostic and clinicopathological significance of NEK2 expression in HCC using a two-part study consisting of a retrospective cohort study and a meta-analysis. Methods: In the cohort study, NEK2 expression in 206 HCC samples and adjacent normal liver tissues was detected by immunohistochemistry (IHC). Patients were divided into a high NEK2 expression group and a low NEK2 expression group by the median value of the immunohistochemical scores. The Kaplan–Meier method with the log-rank test was used to analyze survival outcomes in the two groups, and multivariate analysis based on Cox proportional hazard regression models was applied to identify independent prognostic factors. In the meta-analysis, eligible studies were searched in PubMed, EMBASE, Web of Science, and CNKI databases. STATA version 12.0 (Stata Corporation, College Station, TX) was used for statistical analyses. Results: The IHC results of our cohort study showed higher NEK2 expression in HCC tissues compared with adjacent normal liver tissues. Multivariate analysis revealed that high NEK2 expression was an independent risk factor for poor overall survival (OS) [hazard ratio (HR) = 1.763; 95% CI, 1.060–2.935; P = 0.029] and disease-free survival (DFS) [hazard ratio (HR) = 1.687; 95% CI, 1.102–2.584; P = 0.016] in HCC patients. A total of 11 studies with 1,698 patients were enrolled in the meta-analysis, consisting of 10 studies from the database search and our cohort study. The pooled results revealed that high NEK2 expression correlated closely with poor OS among HCC patients (HR = 1.47; 95% CI, 1.21–1.80; P < 0.01), and DFS/recurrence-free survival (RFS) (HR = 1.92; 95% CI, 1.41–2.63; P < 0.01). Additionally, our meta-analysis also showed that the proportion of HCC patients with high NEK2 expression was greater in the group with larger tumors (> 5 cm) than in the group with smaller tumors (≤ 5 cm) [odds ratio (OR) = 2.02; 95% CI, 1.13–3.64; P < 0.01). Conclusion: Our study demonstrated that high NEK2 expression is a risk factor for poor survival in HCC patients. More prospective, homogeneous, and multiethnic studies are required to validate our findings.

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Increased NEK2 in hepatocellular carcinoma promotes cancer progression and drug resistance by promoting PP1/Akt and Wnt activation

Cited by 28 publications

References 31 publications

Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

MicroRNA‐128 promotes apoptosis in lung cancer by directly targeting NIMA‐related kinase 2

The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study

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