Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression

Wu, Sheng; Lin, Syuan Ling; Lee, Kang Yun; Chuang, Hsiao-Chi; Feng, Po Hao; Cheng, Wanli; Liao, Chien Wei; Cheng, Hsiang; Lin, Yan‐Hui; Tsai, Chun‐Yi; Chen, Wei Jan; Yeh, Chau Ting; Lin, Kwang Huei

doi:10.1002/ijc.30559

Cited by 37 publications

(28 citation statements)

References 40 publications

(48 reference statements)

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“…Finally, NEK2 overexpression contributed to HCC tumor growth, migration, and angiogenesis by pAKT/NF-κB (factor nuclear kappa B). Regarding angiogenesis, NEK2 also induced IL-8 (Interleukin 8) expression [93].…”

Section: Nek2mentioning

confidence: 99%

Checking NEKs: Overcoming a Bottleneck in Human Diseases

et al. 2020

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In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as the cell cycle, cell division, cilia formation, and the DNA damage response. The review of the literature points to the pivotal participation of NEKs in important human diseases, like different types of cancer, diabetes, ciliopathies and central nervous system related and inflammatory-related diseases. The different known regulatory molecular mechanisms specific to each NEK are also presented, relating to their involvement in different diseases. In addition, important information about NEKs remains to be elucidated and is highlighted in this review, showing the need for other studies and research regarding this kinase family. Therefore, the NEK family represents an important group of kinases with potential applications in the therapy of human diseases.

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Section: Nek2mentioning

confidence: 99%

Checking NEKs: Overcoming a Bottleneck in Human Diseases

et al. 2020

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“…Similarly, a study by Wu et al demonstrated that NKE2 overexpression can induce the resistance of hepatoma J7 or Hep3B cells to chemotherapy via upregulation of ABCC10 and the expression of Twist [29]. Additionally, abnormal activation of the p-AKT/NF-κB signaling pathway and matrix metalloproteinase-2 was found to be involved in NEK2 overexpressioninduced migration, invasion, and angiogenesis in HCC [26,29].…”

Section: Discussionmentioning

confidence: 86%

“…ABCG2, a member of ABC transporter family, is a vital element of multi-drug resistance system in cancer [47] and Lin et al demonstrated that NEK2 plays a crucial role in chemotherapeutic resistance by regulating the expression of ABCG2 in HCC cells [27]. Similarly, a study by Wu et al demonstrated that NKE2 overexpression can induce the resistance of hepatoma J7 or Hep3B cells to chemotherapy via upregulation of ABCC10 and the expression of Twist [29]. Additionally, abnormal activation of the p-AKT/NF-κB signaling pathway and matrix metalloproteinase-2 was found to be involved in NEK2 overexpressioninduced migration, invasion, and angiogenesis in HCC [26,29].…”

Section: Discussionmentioning

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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“…The survival rate of HCC is usually poor due to the high probability of tumor recurrence and metastasis after treatment. We therefore urgently need to identify novel therapeutic targets and biomarkers, with the goal of developing effective strategies to improve the prognosis of HCC [5].…”

Section: Introductionmentioning

confidence: 99%

Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

Huang

Lin

Cheng

et al. 2020

Cells

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Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Long non-coding (lnc) RNAs regulate complex cellular functions, such as cell growth, differentiation, metabolism, and metastasis. Although deregulation of lncRNA expression has been detected in HCC, many of the hepato-carcinogenesis-associated lncRNAs remain yet unidentified. Here, we aimed to investigate the involvement of a specific HCC-dysregulated lncRNA, FAM215A, and characterize its molecular regulation mechanism. We show for the first time that FAM215A is overexpressed in HCC, and its expression level correlates with tumor size, vascular invasion, and pathology stage. Overexpression of FAM215A accelerates cell proliferation and metastasis in HCC cells. According to Gene Expression Omnibus Dataset analysis, FAM215A is induced in doxorubicin (DOX)-resistant HCC cells. Overexpression of FAM215A increases DOX resistance in two HCC cell lines, and this is associated with enhanced expression of lysosome-associated membrane protein 2 (LAMP2). FAM215A interacts with LAMP2 to protect it from ubiquitination. Together, our results show that the lncRNA, FAM215A, is highly expressed in HCC, where it interacts with and stabilizes LAMP2 to increase tumor progression while decreasing doxorubicin sensitivity.

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Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression

Cited by 37 publications

References 40 publications

Checking NEKs: Overcoming a Bottleneck in Human Diseases

Checking NEKs: Overcoming a Bottleneck in Human Diseases

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

Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

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